Scolaris Content Display Scolaris Content Display

為重症成年患者開立低熱量營養補給處方

Appendices

Appendix 1. Search strategy for CENTRAL, The Cochrane Library

#1 MeSH descriptor: [Critical Illness] explode all trees
#2 stressed:ti,ab,kw
#3 critical* next ill*:ti,ab,kw
#4 MeSH descriptor: [Critical Care] explode all trees
#5 MeSH descriptor: [Intensive Care Units] explode all trees
#6 #1 or #2 or #3 or #4 or #5
#7 (feeding or food or nutrition* or diet* or intake*) .ti
#8 (eucalor* or hypoenerg* or underfeed* or (low calor*) or hypocalor*):ti,ab,kw
#9 MeSH descriptor: [Diet] explode all trees
#10 MeSH descriptor: [Parenteral Nutrition] explode all trees
#11 MeSH descriptor: [Enteral Nutrition] explode all trees
#12 #7 or #8 or #9 or #10 or #11

Appendix 2. Search strategy for MEDLINE (Ovid SP)

1 exp Critical Illness/
2 stressed.ti,ab.
3 (critical adj3 ill*).mp.
4 Critical Care/
5 Intensive Care/
6 Intensive Care Units/
7 1 or 2 or 3 or 4 or 5 or 6
8 (feeding or food or nutrition* or diet* or intake*).ti.
9 (eucalor* or hypoenerg* or underfeed* or (low adj3 calor*) or h?pocalor*).mp.
10 Diet/ or Parenteral‐Nutrition/ or Enteral‐Nutrition/
11 8 or 9 or 10
12 7 and 11
13 "Randomized Controlled Trial".pt.
14 "Controlled Clinical Trial".pt.
15 randomi?ed.ti,ab.
16 placebo*.ti,ab.
17 "drug therapy".sh.
18 randomly.ti,ab.
19 trial.ti,ab.
20 groups.ti,ab.
21 13 or 14 or 15 or 16 or 17 or 18 or 19 or 20
22 Animals/ not (Humans/ and Animals/)
23 21 not 22
24 12 and 23

Appendix 3. Search strategy for Embase (Ovid SP)

1 eucalor*.ti,ab.
2 hypoenerg*.ti,ab.
3 underfeed*.ti,ab.
4 (low adj3 calor*).ti,ab.
5 h?pocalor*.ti,ab.
6 1 or 2 or 3 or 4 or 5
7 (feeding or food or nutrition* or diet* or intake*).ti.
8 *diet/
9 *parenteral nutrition/
10 6 or 7 or 8 or 9
11 critical*.ti,ab.
12 stressed.ti,ab.
13 *intensive care unit/
14 *intensive care/
15 *critical illness/
16 11 or 12 or 13 or 14 or 15
17 10 and 16
18 random.tw. or placebo.mp. or double‐blind.tw.
19 17 and 18

Appendix 4. Search strategy for LILACS, (BIREME)

(tw:(("ENFERMEDAD CRITICA" OR "UNIDADES DE TERAPIA intensiva" OR "CUIDADOS INTENSIVOS" OR trauma* OR "TRAUMA multiple" OR "SEPSIS" OR septicemia* OR "ENFERMEDAD AGUDA" OR "cuidados criticos" OR "cuidado critico" OR "cuidado intensivo" OR "cuidados intensivos" OR icu* OR uti*)))
AND

(tw:((desnutricion* OR hypocalor* OR hipocalor* OR hypoenerg* OR hipoenerg* OR underfeed* OR subaliment* OR "bajas calorias" OR "bajo valor" OR hiponutr* OR malnutr* OR calorimetr*)))

AND
(instance:"regional") AND (instance:"regional") AND ( db:("LILACS") AND type_of_study:("clinical_trials"))

Appendix 5. Meta‐regression

STATA 14.1 outputs exploring the effect of several explanatory variables on the primary outcomes with the highest number of included studies: mortality in hospital, infectious complications, length of hospital stay and length of ICU stay. The covariates included in the models were: type of participants [typepatient]; calories received by the intervention group in three categories categorized [catcal]; difference in the amount of calories received by the control groups minus the intervention group [difcal].

The explanatory variables were defined as follow:

  1. typepatient: surgical participant vs medical participant (all surgical participants received parenteral nutrition and medical received enteral nutrition) (See Table 1).

  2. catcal: categories denominated by the amount of calories really received by the intervention groups, according to the following: very hypocaloric ≤ 10 kcal/kg/day (icatcal 2); hypocaloric ≥ 10 to < 25 kcal/kg/day (icatcal 1); normocalcaloric or hypercaloric ≥ 25 kcal/kg/day (icatcal 0) (see Table 2).

  3. difcal: absolute difference in kcal/kg/day received by the control minus the intervention groups (see Table 3).

We analysed several different models for each outcome. We only presented the model with the three covariates of each outcome, including the full output of the STATA 14.1 statistics.

In each model the covariates were typed in bold (see above definitions). The other codes in tables were:

  1. logrr: Relative risk of dichotomic outcomes.

  2. ES: Mean difference of continuous outcomes.

  3. Coef.: Value of the relative risk or the mean difference in their units

  4. P > t: Probability that the Logrr difference adjusted by other covariates could be related to chance if P is higher than 0.05

  5. Std. Err: Standard error of the coefficient.

  6. t: test.

  7. P > t: Probability that the Logrr difference adjusted by other covariates could be related to chance if P is higher than 0.05 (not significant).

  8. 95% conf. interval: 95% confidence interval of the Logrr or ES values.

It is important to state the limitations of this meta‐regression because of the limited number of studies for the number of covariates in the model. Meta‐regression should generally not be considered when there are fewer than 10 studies in a meta‐analysis.

1. Mortality in hospital

xi: metareg logrrdifcal i.catcal typepatient, wsse(selogrr) bsest(reml)

i.catcal _Icatcal_0‐2 (naturally coded; _Icatcal_0 omitted)

note: _Icatcal_1 dropped because of collinearity

numerical derivatives are approximate

nearby values are missing

Meta‐regression Number of observations = 7

REML estimate of between‐study variance tau2 = 0

% residual variation due to heterogeneity I‐squared_res = 0.00%

Proportion of between‐study variance explained Adj R‐squared = 100.00%

Joint test for all covariates Model F(3,3) = 1.16

With Knapp‐Hartung modification Prob > F = 0.4542

logrra

Coef.

Std. Err.

t

P > t

(95% Conf.

Interval)

difcal

.0237277

.0333315

0.71

0.528

−.0823481

.1298035

_Icatcal_2

.2621164

.2656104

0.99

0.396

−.5831745

1.107407

typepatient

−.3222415

.8614032

−0.37

0.733

−3.063611

2.419128

_cons

−.2805905

.1894936

−1.48

0.235

−.8836437

.3224628

aRelative Risk

Interpretationof hospital mortality. None of the covariates had a statistically significant influence on the size of the intervention effect on hospital mortality (P > 0.05).

2. Infectious complications

xi: metareg logrr difcal i.catcal typepatient, wsse(selogrr) bsest(reml)

i.catcal _Icatcal_0‐2 (naturally coded; _Icatcal_0 omitted)

Meta‐regression Number of obs = 10

REML estimate of between‐study variance tau2 = .0115

% residual variation due to heterogeneity I‐squared_res = 40.22%

Proportion of between‐study variance explained Adj R‐squared = 24.55%

Joint test for all covariates Model F(4,5) = 1.48

With Knapp‐Hartung modification Prob > F = 0.3346

logrra

Coef.

Std. Err.

t

P > t

(95% Conf. Interval)

difcal

.0660771

.0343893

1.92

0.113

−.0223233

.1544776

_Icatcal_1

−.1032021

.5736509

−0.18

0.864

−1.577819

1.371415

_Icatcal_2

−.511068

.5948386

−0.86

0.430

−2.040149

1.018013

typepatient

−.5686713

.502095

−1.13

0.309

−1.859348

.7220049

_cons

−.209952

.6345331

−0.33

0.754

−1.841071

1.421167

aRelative Risk

Interpretation of infectious complications. None of the covariates had a statistically significant influence on the size of the intervention effect on infectious complications (P > 0.05).

3. Hospital length of stay

xi: metareg _ES difcal i.catcal typepat, wsse(_seES) bsest(reml)

i.catcal _Icatcal_0‐2 (naturally coded; _Icatcal_0 omitted)

Meta‐regression Number of obs = 9

REML estimate of between‐study variance tau2 = .1866

% residual variation due to heterogeneity I‐squared_res = 84.83%

Proportion of between‐study variance explained Adj R‐squared = ‐0.95%

Joint test for all covariates Model F(4,4) = 0.95

With Knapp‐Hartung modification Prob > F = 0.5178

_ESa

Coef.

Std. Err.

t

P > t

(95% Conf.

Interval)

difcal

.0227448

.0664972

0.34

0.750

−.1618811

.2073708

_Icatcal_1

.5450151

.5673605

0.96

0.391

−1.03023

2.12026

_Icatcal_2

−.1219102

.7756573

−0.16

0.883

−2.27548

2.03166

typepat

−.2502513

.5116285

−0.49

0.650

−1.67076

1.170257

_cons

−.3512504

.7353122

−0.48

0.658

−2.392804

1.690304

a Mean difference

Interpretation of length of hospital stay. None of the covariates had a statistically significant influence on the size of the intervention effect on hospital length of stay (P > 0.05).

4. ICU length of stay

xi: metareg _ES difcal i.catcal typepat, wsse(_seES) bsest(reml)

i.catcal _Icatcal_0‐2 (naturally coded; _Icatcal_0 omitted)

note: typepat dropped because of collinearity

Meta‐regression Number of obs = 11

REML estimate of between‐study variance tau2 = .2453

% residual variation due to heterogeneity I‐squared_res = 83.29%

Proportion of between‐study variance explained Adj R‐squared = ‐3.80%

Joint test for all covariates Model F(3,7) = 0.99

With Knapp‐Hartung modification Prob > F = 0.4503

_ESa

Coef.

Std. Err.

t

P > t

(95% Conf.

Interval)

difcal

.0459442

.0578779

0.79

0.453

−.0909154

.1828038

_Icatcal_1

.8943999

.5321506

1.68

0.137

−.3639364

2.152736

_Icatcal_2

.4275402

.5473569

0.78

0.460

−.8667533

1.721834

_cons

−.9390958

.6599035

−1.42

0.198

−2.49952

.621328

aMean difference

Interpretation of length of ICU stay. None of the covariates had a statistically significant influence on the size of the intervention effect on length of ICU stay (P > 0.05).

Appendix 6. Database for meta‐regression

We conducted the meta‐regressions of each of the outcomes according to the following databases. The codes used to identify each column of the databases were:

  1. trialnam: study ID.

  2. cases1: number of events in the intervention group.

  3. cases0: number of events in the control group.

  4. tot1: number of participants in the intervention group.

  5. tot0: number of participants in the control group.

  6. mean 1: mean value in the intervention group.

  7. SD 1: standard deviation in the intervention group.

  8. total 1: total number of participants in the intervention group.

  9. mean 2: mean value in the control group.

  10. SD 2: standard deviation in the control group.

  11. total 2: total number of participants in the control group.

  12. difcal: absolute difference in kcal/kg/day between the control minus the study group.

  13. catcal: categories according the amount of calories received by the intervention groups. 0 ≥ 25 kcal/kg/day; 1 ≥ 10 to < 25 kcal/kg/day; 2 < 10 kcal/kg/day.

  14. typepatient: medical participants 0; surgical participants 1 (also equivalent to enteral nutrition and parenteral nutrition respectively)

  15. n/a: not available.

Database of mortality in hospital

Mortality in hospital

trial name

cases1

tot1

cases0

tot0

difcal

catcal

typepatient

Arabi 2011

36

120

51

120

2.55

1

0

Arabi 2015

108

447

123

445

5.48

1

0

Battistella 1997

2

27

0

30

7

0

1

Charles 2014

3

41

4

42

5

1

0

Choban 1997

0

6

2

7

14

1

1

Ibrahim 2002

20

75

15

75

4.28

2

0

McCowen 2000

2

21

3

19

4.1

1

1

Petros 2016

17

46

17

54

8.4

1

0

Rice 2011

22

98

20

102

13.71

2

0

Database of infectious complications

Infectious complications

trial name

cases1

tot1

cases0

tot0

difcal

catcal

typepatient

Ahrens 2005

5

20

2

20

10.4

0

1

Arabi 2011

53

120

56

120

2.55

1

0

Arabi 2015

161

448

169

446

5.48

1

0

Battistella 1997

13

27

22

30

7

0

1

Charles 2014

23

41

24

42

5

1

0

Ibrahim 2002

23

75

37

75

4.28

2

0

McCowen 2000

6

21

10

19

4,1

1

1

NHLBI 2012

96

508

79

492

11.05

2

0

Petros 2016

13

46

6

54

8.4

1

0

Rice 2011

30

98

33

102

13.71

2

0

Database of length of hospital stay

Length of hospital stay

trial name

Mean 1

SD 1

total 1

mean 2

SD 2

total 2

difcal

catcal

typepatient

Ahrens 2005

23.4

23.92

20

27.8

17.4

20

10.4

0

1

Arabi 2011

70.2

106.9

120

67.2

93.6

120

2.55

1

0

Arabi 2015

48.3

67.7

448

54.4

73.9

446

5.48

1

0

Battistella 1997

27

16

27

39

24

30

7

0

1

Charles 2014

35.2

4.9

41

31

2.5

42

5

1

0

Choban 1997

48

30

6

45

38

7

14

1

1

Ibrahim 2002

16.7

12.5

75

22.9

19.7

75

4.28

2

0

McCowen 2000

19

14

21

17

15

19

4.1

1

1

Norouzy 2013

19.9

11

30

35.6

25

30

n/a

n/a

0

Petros 2016

38.1

33.4

46

27.4

21.9

54

8.4

1

0

Database of length of ICU stay

Length of ICU stay

trial name

mean 1

SD 1

total 1

mean 2

SD 2

total 2

difcal

catcal

typepatient

Ahrens 2005

16.75

10.35

8

23

15.2

10

10.4

0

1

Arabi 2011

11.7

8.1

120

14.5

15.5

120

2.55

1

0

Arabi 2015

15.8

11.6

448

16.4

12.1

446

5.48

1

0

Battistella 1997

18

12

27

29

22

30

7

0

1

Charles 2014

16.7

2.7

41

13.5

1.1

42

5

1

0

Ibrahim 2002

9.8

7.4

75

13.6

14.2

75

4.28

2

0

NHLBI 2012

11.5

11

508

11

9.8

492

11.05

2

0

Petros 2016

22.4

25.5

46

17

16.1

54

8.4

1

0

Rice 2011

8.1

6.1

98

7,6

5.9

102

13.71

2

0

Rugeles 2013

9.5

5.5

40

10.4

5

40

2

1

0

Rugeles 2016

13.23

6.03

60

13.45

8.33

60

7.9

1

0

Updated study flow diagram, 20 June 2017
Figuras y tablas -
Figure 1

Updated study flow diagram, 20 June 2017

Ir a la figura de la revisiónAbrir en una pestaña nueva

Risk of bias graph: review authors' judgements about each risk of bias domain presented as percentages across all included studies.
Figuras y tablas -
Figure 2

Risk of bias graph: review authors' judgements about each risk of bias domain presented as percentages across all included studies.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Risk of bias summary: review authors' judgements about each risk of bias domain for each included study. Red colour represents high risk of bias; green, low risk of bias; and yellow, unclear risk of bias.
Figuras y tablas -
Figure 3

Risk of bias summary: review authors' judgements about each risk of bias domain for each included study. Red colour represents high risk of bias; green, low risk of bias; and yellow, unclear risk of bias.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Funnel plot of comparison: 1 Hypocaloric nutrition (intervention) vs. Control, outcome: 1.1 Mortality in hospital.
Figuras y tablas -
Figure 4

Funnel plot of comparison: 1 Hypocaloric nutrition (intervention) vs. Control, outcome: 1.1 Mortality in hospital.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Comparison 1 Hypocaloric nutrition (intervention) vs. Control, Outcome 1 Mortality in hospital.
Figuras y tablas -
Analysis 1.1

Comparison 1 Hypocaloric nutrition (intervention) vs. Control, Outcome 1 Mortality in hospital.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Comparison 1 Hypocaloric nutrition (intervention) vs. Control, Outcome 2 Mortality in ICU.
Figuras y tablas -
Analysis 1.2

Comparison 1 Hypocaloric nutrition (intervention) vs. Control, Outcome 2 Mortality in ICU.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Comparison 1 Hypocaloric nutrition (intervention) vs. Control, Outcome 3 Mortality at 30 days.
Figuras y tablas -
Analysis 1.3

Comparison 1 Hypocaloric nutrition (intervention) vs. Control, Outcome 3 Mortality at 30 days.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Comparison 1 Hypocaloric nutrition (intervention) vs. Control, Outcome 4 Length of Hospital stay (days).
Figuras y tablas -
Analysis 1.4

Comparison 1 Hypocaloric nutrition (intervention) vs. Control, Outcome 4 Length of Hospital stay (days).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Comparison 1 Hypocaloric nutrition (intervention) vs. Control, Outcome 5 Length of ICU stay (days).
Figuras y tablas -
Analysis 1.5

Comparison 1 Hypocaloric nutrition (intervention) vs. Control, Outcome 5 Length of ICU stay (days).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Comparison 1 Hypocaloric nutrition (intervention) vs. Control, Outcome 6 Infectious complications.
Figuras y tablas -
Analysis 1.6

Comparison 1 Hypocaloric nutrition (intervention) vs. Control, Outcome 6 Infectious complications.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Comparison 1 Hypocaloric nutrition (intervention) vs. Control, Outcome 7 Length of mechanical ventilation (days).
Figuras y tablas -
Analysis 1.7

Comparison 1 Hypocaloric nutrition (intervention) vs. Control, Outcome 7 Length of mechanical ventilation (days).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Comparison 1 Hypocaloric nutrition (intervention) vs. Control, Outcome 8 Non‐infectious complications (diarrhoea).
Figuras y tablas -
Analysis 1.8

Comparison 1 Hypocaloric nutrition (intervention) vs. Control, Outcome 8 Non‐infectious complications (diarrhoea).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Comparison 1 Hypocaloric nutrition (intervention) vs. Control, Outcome 9 Hyperglycaemia.
Figuras y tablas -
Analysis 1.9

Comparison 1 Hypocaloric nutrition (intervention) vs. Control, Outcome 9 Hyperglycaemia.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Comparison 1 Hypocaloric nutrition (intervention) vs. Control, Outcome 10 Hypoglicaemia.
Figuras y tablas -
Analysis 1.10

Comparison 1 Hypocaloric nutrition (intervention) vs. Control, Outcome 10 Hypoglicaemia.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Comparison 1 Hypocaloric nutrition (intervention) vs. Control, Outcome 11 Nitrogen balance (g/day).
Figuras y tablas -
Analysis 1.11

Comparison 1 Hypocaloric nutrition (intervention) vs. Control, Outcome 11 Nitrogen balance (g/day).

Ir a la figura de la revisiónAbrir en una pestaña nueva
Summary of findings for the main comparison. Hypocaloric nutrition compared to control for critically‐ill adults

Hypocaloric nutrition compared to control for critically‐ill adults

Patient or population: critically‐ill adults
Settings: Hospitals (intensive care units), eight in USA, two in Colombia, one in Saudi Arabia and Canada, and one each in Saudi Arabia, Germany, Greece and Iran
Intervention: hypocaloric nutrition

Comparison: control nutritional support with a higher caloric intake than the 'intervention' group

Outcomes

Effect estimate (range of results of individual studies)

N of Participants
(studies)

Quality of the evidence
(GRADE)

Mortality in hospital: death occurring during the hospital stay

Range of risk ratios from 0.23 to 5.54a

1775

(9 studies)

⊕⊕⊝⊝
very lowb,c,d

Mortality in ICU: death occurred during the ICU stay

Range of risk ratios from 0.81 to 5.54a

1291
(4 studies)

⊕⊕⊝⊝
very lowb,c,d

Mortality at 30 days: 28 to 30 days all‐cause mortality

Range of risk ratios from 0.79 to 3.00a

2611
(7 studies)

⊕⊕⊝⊝
very lowb,c,d

Length of hospital stay: days stayed in the hospital

Range of length of hospital stay from 15.70 days lower to 10.70 days highera

1677
(10 studies)

⊕⊝⊝⊝
very lowb,c,e

Length of ICU stay: days stayed in the ICU

Range of length of ICU stay from 11.00 days lower to 5.40 days highera

2942
(11 studies)

⊕⊝⊝⊝
very lowb,c,e

Infectious complications: events of any type of infectious complications occurred during the hospital stay, registered by the study authors according to their diagnostic criteria of infections.

Range of risk ratios from 0.54 to 2.54a

2804
(10 studies)

⊕⊝⊝⊝
very lowb,c,e

Length of mechanical ventilation: days on mechanical ventilation during ICU stay

Range of mean differences: 13.20 days lower to 8.36 days highera

3000

(12 studies)

⊕⊝⊝⊝
very lowb,c,e

GRADE Working Group grades of evidence
High quality: further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: we are very uncertain about the estimate.

aResults were not combined due to clinical heterogeneity.
bDowngraded one level due to risk of bias: most studies had unclear or high risk of bias.
cDowngraded one level due to imprecision issues: very wide confidence intervals.
dDowngraded one level due to inconsistency: wide variance of point estimates across studies.
eDowngraded one level due to inconsistency: high statistical heterogeneity I2 > 50%.

Figuras y tablas -
Summary of findings for the main comparison. Hypocaloric nutrition compared to control for critically‐ill adults
Ir a la tabla de la revisión
Table 1. Differences in participants, interventions and outcomes across included studies

Study ID

Type of participants

Primary outcomes

Arm

Number of ICU participants

APACHE II score mean ± SD

Route (enteral or parenteral)

Duration of PN or EN (days)

Mechanical ventilation

(% of participants)

ICU mortality %

Hospital mortality %

Ahrens 2005

Surgical participants with PN requirement

Incidence/severity hyperglycaemia and insulin received by the participants

Hypoc.

8 (other 12 non‐ICU)

20 ± 9

Parenteral

6 (4 to 10)

100

Not reported

Not reported

Control

10 (other 10 non‐ICU)

19 ± 11

7 (5 to 10)

80

Arabi 2011

Medical (mainly) and surgical participants with EN. 2 x 2 factorial trial with Intensive Insuline therapy

28 days all‐cause mortality

Hypoc.

120

25 ± 8

Enteral

Not reported

99

18

30

Control

120

25 ± 8

99

22

43

Arabi 2015

Critically‐ill participants (75% medical)

90‐day all‐cause mortality

Hypoc.

448

21 ± 7.9

Enteral

9.1 ± 4.6

97.3

16.1

24.2

Control

446

21 ± 8.2

9.4 ± 4.4

96.2

19.1

27.6

Battistella 1997

Trauma participants with PN requirement

Length of hospital stay, length of stay in the ICU, number of days on mechanical ventilation and infectious complications.

Hypoc.

27

22 ± 5

Parenteral

10

Not reported

7.4

Not reported

Control

30

23 ± 6

10

0

Charles 2014

Critically‐ill surgical participants

Hospital‐acquired infection

Hypoc.

41

16.6 ± 0.9

Enteral & parenteral

12.6 ± 2.8

68

N/A

7.3

Control

42

17.3 ± 0.8

10.4 ± 1.1

57

N/A

9.5

Choban 1997

Obese participants with PN requirement. Predominantly surgical diseases

Achievement of nitrogen balance

Hypoc.

6 (other 10 non‐ICU)

13 ± 5

Parenteral

10 ± 3

Not reported

Not reported

0

Control

7 (other 7 non‐ICU)

15 ± 5

11 ± 2

28.6

Ibrahim 2002

Medical ICU participants with EN

Incidence of ventilator‐associated pneumonia

Hypoc.

75

26 ± 8

Enteral

5 ± 6

100

Not reported

27

Control

75

25 ± 8

10 ± 12

100

20

McCowen 2000

Participants with predominantly surgical diseases requiring PN

Glycaemic control and Infections

Hypoc.

21

not reported

Parenteral

≥ 5

50

10

Not reported

Control

19

not reported

≥ 5

33

16

NHLBI 2012

Acute lung injury predominantly due to medical diseases (61% and 63% of participants) with EN

Ventilator‐free days at study day 28

Hypoc.

508

APACHE III 92 ± 28

Enteral

6

100

Not reported

22.4

Control

492

APACHE III 90 ± 27

Enteral

6

100

19.6

Norouzy 2013

Critically‐ill head trauma participants

28 days of all‐cause mortality

Hypoc.

30

Not reported

Enteral

7

Not reported

Not reported

10.7a

Control

30

7

3.8a

Petros 2016

Medical ICU with EN and/or PN requirement

Glycaemic control and mortality

Hypoc.

46

31 ± 9

Enteral & parenteral

7

not reported

22

37

Control

54

28 ± 8

7

22

31

Rice 2011

Acute lung injury, predominantly due to medical diseases with EN

Ventilator‐free days at study day 28

Hypoc.

98

27 ± 8

Enteral

6 ± 4

100

Not reported

22

Control

102

27 ± 7

5 ± 3

100

20

Rugeles 2013

Medical ICU participants with EN requirement

Change in SOFA score at 48 hours

Hypoc.

40

14 ± 5

Enteral

7

Not reported

Not reported

Not reported

Control

40

15 ± 6

Rugeles 2016

Medical ICU participants with EN requirement

Change in SOFA score at 48 hours

Hypoc.

60

13.5 ± 6.4

Enteral

7

Not reported

Not reported

30a

Control

60

13.7 ± 6.8

27a

Theodorakopoulou 2016

Septic, mechanically ventilated critically‐ill participants

28‐day mortality

Hypocal.

Total sample of 74 participants

Total sample

22 ± 4

Enteral

Not reported

Not reported

Not reported

Not reported

Control

a28‐day mortality.

EN = Enteral nutrition; ICU = Intensive Care Unit; N/A: not available; PN = Parenteral nutrition; SOFA = Sequential Organ Failure Assessment

Figuras y tablas -
Table 1. Differences in participants, interventions and outcomes across included studies
Ir a la tabla de la revisión
Table 2. Calories and protein received in both study groups

Studies

How data was reported

Hypocaloric

(intervention)

group

Control group

Calories received by the

"hypocaloric" intervention

group (kcal/kg/day)

Calories received by the

"normocaloric" control

group (kcal/kg/day)

Categories denominated by the calories really

received in the intervention and

the control groups a

Ahrens 2005

Total calories/kg/day (median (IQ))b

26.6 (26.2 to 27.5)

37 (36.0 to 38.4)

26.60 (median)

37.00 (median)

Normocaloric vs hypercaloric

Protein g/kg/day (mean± SD)

1.61 ± 0.13

1.53 ± 0.26

Arabi 2011

Calories/day (mean ± SD)

1066.6 ± 306.1

1251.7 ± 432.5

13.85

16.40

Hypocaloric vs hypocaloric

Protein g/day (mean ± SD)

47.5 ± 21.2

43.6 ± 18.9

Arabi 2015

Calories/day (mean ± SD)

835 ± 297

1299 ± 2470

10.56

16.04

Hypocaloric vs hypocaloric

Protein g/day (mean ± SD)

57 ± 24

59 ± 25

Battistella 1997

Calories/kg ideal body weight/day (mean ± SD)

27.4 ± 2

34.4 ± 2

27.4 (of ideal body weight)

34.4 (of ideal body weight)

Normocaloric vs. normocaloric

Protein g/kg ideal body weight/day (mean± SD)

1.6 ± 0.1

1.6 ± 0.2

Charles 2014

Calories/kg/day (mean ± SD)

12.3 ± 0.7

17.1 ± 1.1

12

17

Hypocaloric vs hypocaloric

Protein g/kg/day (mean ± SD)

1.1 ± 0.1

1.1 ± 0.1

Choban 1997

Kcal/kg actual body weight/day (mean ± SD)

Kcal/kg ideal body weight/day (mean ± SD)

8.6 ± 2.39

13.88 ± 2.87

17.45 ± 4.06

27.99 ± 3.83

14.00 (of ideal body weight)

28.00 (of ideal body weight)

Hypocaloric vs normocaloric

Protein g/kg actual body weight/day (mean ± SD)

Protein g/kg ideal body weight/day (mean ± SD)

1.2 ± 0.2

2.0 ± 0.1

1.2 ± 1.2

2.0 ± 0.1

Ibrahim 2002

Calories/day (mean ± SD)

126 ± 115

474 ± 400

1.53

5.81

Very hypocaloric vs very hypocaloric

Proteins g/day (mean) (mean ± SD)

5.3 ± 5.3

18.7 ± 15.4

McCowen 2000

Calories/kg/day (mean ± SD)

14 ± 3

18 ± 4

14.30

18.40

Hypocaloric vs hypocaloric

Proteins g/kg/day (mean ± SD)

1.1 ± 0.2

1.3 ± 0.2

NHLBI 2012

Calories/day (mean ± SD)

399 ± 225

1365 ± 596

4.64 (estimated by kcal/day divided

by weight from the baseline table)

15.69 (estimated by kcal/day divided

by weight from the baseline table)

Very hypocaloric vs hypocaloric

Proteins: information not collected

‐

‐

Norouzy 2013

Calories/kg/day (mean ± SD)

Not reported

Not reported

N/A

N/A

N/A

Protein g/kg/day (mean ± SD)

Not reported

Not reported

Petros 2016

Calories/kg/day (mean ± SD)

11.3 ± 3.1

19.7 ± 5.7

11.30

19.70

Hypocaloric vs hypocaloric

Protein

Data not reported

Data not reported

Rice 2011

Calories/day (mean ± SD of study days 1 to 5)

300 ± 149

1418 ± 686

3.60

17.31

Very hypocaloric vs hypocaloric

Proteins g/day (mean ± SD of study days 1 to 5)

10.9 ± 6.8

54.4 ± 33.2

Rugeles 2013

Calories/kg/day (mean ± SD)

12 ± 3.9

14 ± 6.2

12.00

14.00

Hypocaloric vs hypocaloric

Protein g/kg/day (mean ± SD)

1.4 ± 0.44

0.76 ± 0.32

Rugeles 2016

Total calories/kg ideal body weight/day (mean ± SD)

12.6 ± 3.4

20.5 ± 5.1

13

21

Hypocaloric vs hypocaloric

Protein g/kgIBW/day (mean ± SD)

1.4 ± 0.4

1.4 ± 0.3

Theodorakopoulou 2016

Calories/day (mean ± SD)

962 ± 314

1308 ± 513

Not reported

Estimatedc

16.63 kcal/kg/day

Not reported

Estimatedc

22.62 kcal/kg/day

Estimatedc

Hypocaloric vs normocaloric

Protein g/day

(mean ± SD)

57 ± 24

59 ± 25

Not reported

Estimatedc

0.99 g/kg/day

Not reported

Estimatedc

1.02 g/kg/day

aCategories denominated by the amount of calories really received by both study groups, according to the following: very hypocaloric = < 10 kcal/kg/day; hypocaloric = ≥ 10 to < 25 kcal/kg/day; normocaloric = ≥ 25 to < 35 kcal/kg/day; hypercaloric = ≥ 35 kcal/kg/day.
bIQ: interquartile range ‐ Median total calories received by all 20 participants (ICU and non‐ICU participants) in each group (the total calories received by the 8 and 10 ICU participants in each group were not reported).
cNot reported in the abstract. The numbers are a crude estimation of kcal and grams of protein/kg/day from the whole sample data of height and BMI.

BMI = Body Mass Index; g = gram; ICU = Intensive Care Unit; kcal = kilocalories; N/A: not available; SD = standard deviation; vs = versus

Figuras y tablas -
Table 2. Calories and protein received in both study groups
Ir a la tabla de la revisión
Table 3. Main outcomes in individual studies ordered by the magnitude of the differences in calories received between the control and hypocaloric groups

Study

Difference in calories

between groups

(kcal/kg/day)

Hospital mortality

(%)

IG vs CG

ICU mortality

(%)

IG vs CG

Mortality at 30 days

(%)

IG vs CG

Infectious

complications

(%)

IG vs CG

Length of hospital

stay

(days)a

IG vs CG

ICU length

of stay (days)a

IG vs CG

Length of

mechanical

ventilation (days)a

IG vs CG

Categories denominated by the calories really

received in the intervention and

the control groupsb

Rugeles 2013

2.00

N/A

N/A

N/A

N/A

N/A

9.5 vs 10.4

8.5 vs 9.7

Hypocaloric vs hypocaloric

Arabi 2011

2.55

30% vs 42.5%

17.5% vs 21.7%

18.3% vs 23.3%

44.2% vs 46.7%

70.2 vs 67.2

11.7 vs 14.5

10.6 vs 13.2

Hypocaloric vs hypocaloric

McCowen 2000

4.10

9.5% vs 15.8%

N/A

N/A

28.6% vs 52.6%

19 vs 17

N/A

N/A

Hypocaloric vs hypocaloric

Ibrahim 2002

4.28

26.7% vs 20%

N/A

N/A

30.7% vs 49.3%

16.7 vs 22.9

9.8 vs 13.6

8.1 vs 12.9

Very hypocaloric vs very hypocaloric

Charles 2014

5.00

7.3% vs 9.5%

N/A

N/A

56.1% vs 57.1%

35.2 vs 31

16.7 vs 13.6

10.8 vs 8.3

Hypocaloric vs hypocaloric

Arabi 2015

5.48

24.2% vs 27.6%

16.1% vs 19.1%

20.8% vs 21.8%

35.9% vs 37.9%

48.3 vs 54.4

15.8 vs 16.4

11.3 vs 13.5

Hypocaloric vs hypocaloric

Battistella 1997

7.00

7.4% vs 0%

7.4% vs 0%

N/A

48.2% vs 73.3%

27 vs 39

18 vs 29

15 vs 27

Normocaloric vs normocaloric

Rugeles 2016

7.90

N/A

N/A

30% vs 26.7%

N/A

N/A

13.2 vs 13.5

10.8 vs 10.8

Hypocaloric vs hypocaloric

Petros 2016

8.40

37% vs 31.5%

21.7% vs 22.2%

39.1% vs 33.3%

28.3% vs 11.1%

38.1 vs 27.4

22.4 vs 17

20.7 vs 12.4

Hypocaloric vs hypocaloric

Ahrens 2005

10.40

N/A

N/A

N/A

25% vs 10%

23.4 vs 27.8

16.8 vs 23

11.1 vs 20.3

Normocaloric vs hypercaloric

NHLBI 2012

11.05

N/A

N/A

19.5% vs 19.3%

18.9% vs 16.1%

N/A

11.5 vs 11

10.5 vs 10.2

Very hypocaloric vs hypocaloric

Rice 2011

13.71

22.4% vs 19.6%

N/A

22.4% vs 19.6%

30.6% vs 32.4%

N/A

8.1 vs 7.6

5.7 vs 6.2

Very hypocaloric vs hypocaloric

Choban 1997

14.00

0% vs 29%

N/A

N/A

N/A

48 vs 45

N/A

N/A

Hypocaloric vs normocaloric

Norouzy 2013

N/A

N/A

N/A

10% vs 3.3%

N/A

19.9 vs 35.6

N/A

4.7 vs 17.9

N/A

Theodorakopoulou 2016

N/A

N/A

N/A

18.4% vs

28.9%

N/A

N/A

N/A

N/A

Hypocaloric vs normocaloric

aLengths of hospital, ICU stays and of mechanical ventilation presented in mean days.
bCategories denominated by the amount of calories really received by both study groups, according to the following: very hypocaloric = < 10 kcal/kg/day; hypocaloric = ≥ 10 to < 25 kcal/kg/day; normocaloric = ≥ 25 to < 35 kcal/kg/day; hypercaloric = ≥ 35 kcal/kg/day.

IG = Intervention Group; CG = Control Group; N/A = Not available; vs = versus
Figuras y tablas -
Table 3. Main outcomes in individual studies ordered by the magnitude of the differences in calories received between the control and hypocaloric groups
Ir a la tabla de la revisión
Table 4. Subgroup analyses

Subgroup

N participants (n studies)

Subgroup testing

1. Nutrition status

1.1. Length of hospital stay

Obese

13 (1 RCT)

I2 = 0%, P = 0.76

General

1664 (9 RCTs)

2. Route of nutrition support

2.1. Length of hospital stay

Parenteral

150 (4 RCTs)

I2 = 0%, P = 0.72

Enteral

1725 (6 RCTs)

2.2. Length of ICU stay

Parenteral

75 (2 RCTs)

I2 = 83.3%, P < 0.01

Enteral

2867 (9 RCTs)

2.3. Infectious complications

Parenteral

137 (3 RCTs)

I2 = 0%, P = 0.35

Enteral

2667 (7 RCTs)

2.4. Length of mechanical ventilation

Parenteral

73 (2 RCTs)

I2 = 85.4%, P < 0.01

Enteral

2927 (10 RCTs)

3. Type of participant

3.1. Length of hospital stay

Surgical participants

223 (5 RCTs)

I2 = 0%, P = 0.55

Medical participants

1354 (5 RCTs)

3.2. Length of ICU stay

Surgical participants

158 (3 RCTs)

I2 = 0%, P = 0.52

Medical participants

2784 (8 RCTs)

3.3. Infectious complications

Surgical participants

220 (4 RCTs)

I2 = 0%, P = 0.45

Medical participants

2584 (6 RCTs)

3.4. Length of mechanical ventilation

Surgical participants

156 (3 RCTs)

I2 = 0%, P = 0.45

Medical participants

2854 (9 RCTs)

4. Amount of calories received by each study group

4.1. Length of hospital stay

Normo‐hypercaloric

97 (2 RCTs)

I2 = 84.1%, P < 0.01

Hypocaloric

1370 (6 RCT)

Very hypocaloric

150 ( RCT)

4.2. Length of ICU stay

Normo‐hypercaloric

75 (2 RCTs)

I2 = 0%, P = 0.42

Hypocaloric

1517 (6 RCTs)

Very hypocaloric

1350 (3 RCTs)

4.3. Infectious complications

Normo‐hypercaloric

97 (2 RCTs)

I2 = 0%, P = 0.94

Hypocaloric

1357 (5 RCTs)

Very hypocaloric

1350 (3 RCTs)

4.4. Length of mechanical ventilation

Normo‐hypercaloric

73 (2 RCTs)

I2 = 73.1%, P = 0.02

Hypocaloric

1517 (6 RCTs)

Very hypocaloric

1350 (3 RCTs)

RCT = randomized controlled trial; ICU = Intensive care unit
Figuras y tablas -
Table 4. Subgroup analyses
Ir a la tabla de la revisión
Comparison 1. Hypocaloric nutrition (intervention) vs. Control

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Mortality in hospital Show forest plot

9

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

2 Mortality in ICU Show forest plot

4

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

3 Mortality at 30 days Show forest plot

7

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

4 Length of Hospital stay (days) Show forest plot

10

Mean Difference (IV, Random, 95% CI)

Totals not selected

5 Length of ICU stay (days) Show forest plot

11

Mean Difference (IV, Random, 95% CI)

Totals not selected

6 Infectious complications Show forest plot

10

Risk Ratio (M‐H, Random, 95% CI)

Totals not selected

7 Length of mechanical ventilation (days) Show forest plot

12

Mean Difference (IV, Random, 95% CI)

Totals not selected

8 Non‐infectious complications (diarrhoea) Show forest plot

3

Risk Ratio (M‐H, Random, 95% CI)

Totals not selected

9 Hyperglycaemia Show forest plot

6

Risk Ratio (M‐H, Random, 95% CI)

Totals not selected

10 Hypoglicaemia Show forest plot

5

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

11 Nitrogen balance (g/day) Show forest plot

3

Mean Difference (IV, Random, 95% CI)

Totals not selected
Figuras y tablas -
Comparison 1. Hypocaloric nutrition (intervention) vs. Control
Ir a la tabla de la revisión