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重症成人への低カロリー栄養補給処方

Información

DOI:
https://doi.org/10.1002/14651858.CD007867.pub2Copiar DOI
Base de datos:
  1. Cochrane Database of Systematic Reviews
Versión publicada:
  1. 04 junio 2018see what's new
Tipo:
  1. Intervention
Etapa:
  1. Review
Grupo Editorial Cochrane:
  1. Grupo Cochrane de Atención crítica y de emergencia

Copyright:
  1. Copyright © 2018 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Autores

  • Mario I Perman

    Correspondencia a: Argentine Cochrane Centre, Instituto Universitario Hospital Italiano, Buenos Aires, Argentina

    [email protected]

    [email protected]

  • Agustín Ciapponi

    Argentine Cochrane Centre, Institute for Clinical Effectiveness and Health Policy (IECS‐CONICET), Buenos Aires, Argentina

  • Juan VA Franco

    Argentine Cochrane Centre, Instituto Universitario Hospital Italiano, Buenos Aires, Argentina

  • Cecilia Loudet

    Department of Intensive Care, Universidad Nacional de La Plata, Buenos Aires, Argentina

    Department of Applied Pharmacology, Universidad Nacional de La Plata, Buenos Aires, Argentina

  • Adriana Crivelli

    Unit of Nutrition Support and Malabsorptive Diseases, Hospital HIGA San Martín, La Plata, Argentina

  • Virginia Garrote

    Biblioteca Central, Instituto Universitario Hospital Italiano, Buenos Aires, Argentina

  • Gastón Perman

    Argentine Cochrane Centre, Instituto Universitario Hospital Italiano, Buenos Aires, Argentina

    Department of Medicine, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina

Contributions of authors

Conception, design and coordination of the review: Mario I Perman (MP)
Design of search strategies: Virginia Garrote (VG), MP, Agustín Ciapponi (ACi)
Searching: VG, MP
Manual searches: Cecilia Loudet (CL), Adriana Crivelli (ACr), VG and MP.
Screening search results: MP, CL, ACr.
Organizing retrieval of papers: VG, MP.
Obtaining copies of trials: MP, ACr, CL, GP, VG
Screening retrieved paper against inclusion criteria: MP, CL, ACr, GP.
Selection of trials to include: MP, CL, ACr, GP.
Appraising quality of papers: GP, CL, AC, Juan Franco (JF).
Extracting data from trials: MP, CL, ACr.

Meta‐regression in STATA 14.1 AC
Writing to authors of papers for additional information: MP.

Data management for the review

Entering data into RevMan: MP, GP, ACi.
Analysis of data: MP, ACi, GP, CL, ACr, JF.
Interpretation of data: MP, GP, ACi, CL, JF.
Providing a methodological perspective: ACi, JF.
Providing a clinical perspective: MP, GP, ACi, CL.
Writing the review: MP, ACi, GP, CL, JF.
Update of the review: MP.

Sources of support

Internal sources

  • None, Argentina.

External sources

  • None, Argentina.

Declarations of interest

Mario I Perman received honoraria from laboratory Fresenius‐Kabi S.A (Buenos Aires‐Argentina) for doing educational activities in the field of parenteral nutrition in different clinical settings. He has not received any type of financial support from Fresenius‐Kabi S.A. for doing or writing this Cochrane review.

Agustín Ciapponi: none declared.

Cecilia Loudet: none declared.

Adriana Crivelli: none declared.

Virginia Garrote: none declared.

Gastón Perman: none declared.

Juan VA Franco: none declared.

Acknowledgements

During the prepublication editorial process, the protocol has been commented on by a content editor and two peer reviewers (who are external to the editorial team), members of the Cochrane Consumer network’s international panel of consumers and the Anaesthesia Group’s Information Specialist. For that, we thank Martha Delgado, Khursheed Jeejeebhoy, Alison Avenell, Anne E. Fonfa and Janet Wale. We are especially grateful to Jane Cracknell for her help and patience during the protocol development (Perman 2009), and publication process, to Karen Hovhannisyan and Daniel Comandé for their help with the search strategies and obtaining copies of trials, and to Marit Johansen for the SciSearch information.

We also thank Kursheed Jeejeebhoy, Mette Berger, Roland Dickerson, José F. Patiño, Ewald Schlotzer (Fresenius‐Kabi AG, Germany); Rolf Franke and Ute Brauer (B Braun Melsungen AG, Germany) for their help in suggesting potential studies to be considered, and to the first authors of several trials for giving all the information requested to complete the data for this review: Christine Ahrens sent information on length of ICU and hospital stay and on mechanical ventilation expressed as mean and standard deviation (Ahrens 2005); Sirak Petros completed the data of their initially unpublished but finished pilot study (Petros 2016); Todd Rice, for his own study (Rice 2011) and on behalf of the ARDS Network (NHLBI 2012) gave us important additional information and interpretation of results of both trials; Saúl Rugeles (Rugeles 2013), sent the final version of the trial before it was published and also additional information about participants with hyperglycaemia and to estimate the risks of bias. He also sent us in advance the full paper of his second trial (Rugeles 2016), with some additional information; Yaseen Arabi (Arabi 2015) sent us means and standard deviations of several outcomes; Eric Charles (Charles 2014) sent us the mean and standard deviation value of length of mechanical ventilation and additional information to complete the 'Risk of bias' table.

During the preparation of the final manuscript, we received several comments and advice. We would like to thank Rodrigo Cavallazzi (content editor) and Harald Herkner (content and co‐ordinating editor), Nathan Pace (statistical editor), Bill Simpson, Khursheed Jeejeebhoy, Thomas Bongers (peer reviewers), Janet Wale (consumer editor) and Daren Heyland for their help and editorial advice during the preparation of this systematic review. Once more, we also want to express our special gratitude to Jane Cracknell (Managing Editor) for her help during the editorial process and to Nathan Pace (statistical editor) for his advice about how to perform and report several statistical results.

Version history

Published

Title

Stage

Authors

Version

2018 Jun 04

Prescribed hypocaloric nutrition support for critically‐ill adults

Review

Mario I Perman, Agustín Ciapponi, Juan VA Franco, Cecilia Loudet, Adriana Crivelli, Virginia Garrote, Gastón Perman

https://doi.org/10.1002/14651858.CD007867.pub2

2009 Jul 08

Prescribed hypocaloric nutrition support for critically ill adults

Protocol

Mario I Perman, Agustín Ciapponi, Adriana Crivelli, Virginia Garrote, Cecilia Loudet, Gastón Perman

https://doi.org/10.1002/14651858.CD007867

Differences between protocol and review

Background section

  1. The original Background section contained a single description without subheadings. We updated the references and divided them into level two subheadings according to the Cochrane Handbook for Systematic Reviews of Interventions recommendations (Higgins 2011).

Objectives and outcomes

  1. Modifications in order to comply with the latest MECIR standards (Higgins 2016): we modified the wording of the objectives in order to comply with Standard R5 and R22; we provided additional detail for the definition of outcomes in order to comply with Standard R32; we provided detail on the GRADE methods in order to comply with Standard C23 and R98; we provided detail on subgroup analysis (Standard R52)

  2. In order to have only three primary outcomes (according to Higgins 2011), we changed the order of the primary and secondary outcomes stated in the protocol (Perman 2009), while maintaining all the predefined ones. The primary outcomes for this review were: mortality (in hospital, in lCU and at 30 days); length of stay (in hospital and in ICU) and infectious complications. The secondary outcomes we were able to evaluate were: length of mechanical ventilation, non‐infectious complications, carbohydrate metabolic outcomes (hyperglycaemia, hypoglycaemia), protein metabolic outcomes (nitrogen balance). However, we include seven outcomes in the 'Summary of findings' table. These main outcomes were considered for the subgroup analysis.

Criteria for inclusion of studies

  1. We provided further detail on the inclusion criteria for the Types of interventions that initially was broadly defined as " 1) normo‐ or hypercaloric NS: equal or more than the measured REE or 25 kcal/kg/day (with the same characteristics as above); or 2) no nutrition support at all: fasting or dextrose solutions". We added "We evaluated results of trials designed to compare prescribed hypocaloric enteral or parenteral nutrition support (or permissive underfeeding) with standard nutrition support, or with no nutrition, even if those trials did not reach their caloric goals in the intervention or control groups (intention‐to treat analysis). We did not include trials that planned to provide full nutrition support but resulted in unintended hypocaloric provision (for any reason)."

Search methods

In Electronic searches we made some changes: we applied the trial filter for therapy, maximizing sensitivity developed by HIRU (Health Information Research Unit at McMaster University: hiru.mcmaster.ca/hiru/HIRU_Hedges_EMBASE_Strategies.aspx. We consulted the following trial registries: ClinicalTrials.Gov: clinicaltrials.gov/ct2/home; International Clinical Trials Registry Platform (WHO): apps.who.int/trialsearch/); and ISRCTN Registry: www.isrctn.com/. The LILACS strategy was improved (Appendix 4). We did not perform ISI SciSearch due to lack of access to the database. We did not contact relevant societies to identify abstracts, since we checked the conference proceedings of those societies directly.

Data collection and analysis

  1. We updated the sections Selection of studies, Data extraction and management, Assessment of risk of bias in included studies according to the latest MECIR standards (2016) and Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). They were initially in different subheadings and now use the current recommended subheadings.

  2. We added the sections Measures of treatment effect, Unit of analysis issues, Dealing with missing data and Assessment of reporting biases that were not present in the original protocol.

  3. We constructed the section Assessment of heterogeneity and Data synthesis with the information present in "Analysis" in the original protocol.

  4. We modified the sections Assessment of heterogeneity and Data synthesis, to adjust the cut‐off points to classify and report heterogeneity according to Higgins 2011 (Section 9.5.2).

  5. We added a section for the methods used to develop the 'Summary of findings' table using the GRADE approach (see Sensitivity analysis).

Methods not implemented

  1. Several outcomes stated in the protocol were not reported in the trials; for this reason we were not able to conduct some predefined subgroup analyses. We did a subgroup analysis not prespecified in the protocol to assess the effect of the route of nutrition support (enteral or parenteral). We considered this to be relevant after the search strategy was performed, but before we had conducted any analysis.

Post hoc analysis

  1. After collecting the data about the calories received by both groups of participants in the included studies, and before the analysis of results, we decided to perform the subgroup analysis of the amount of calories received according to the following categories: very hypocaloric, hypocaloric, normocaloric and hypercaloric.

  2. We performed two sensitivity analyses not previously stated in the protocol. In one of them we excluded three studies (Ibrahim 2002; NHLBI 2012; Rice 2011) with a different primary goal: they evaluated early initiation of low‐dose enteral nutrition (hypocaloric trophic feeding) against full enteral dose from the beginning (normocaloric standard feeding). In the other sensitivity analysis, we excluded a study (Battistella 1997), primarily designed to compare parenteral nutrition without the administration of intravenous lipid emulsion (hypocaloric) and with lipids (normocaloric).

  3. When we found high levels of clinical and statistical heterogeneity, we performed a non‐prespecified meta‐regression using STATA 13.1 to explore the effect of several covariates on the main outcomes (Appendix 5).

Change in authorship

  1. Juan VA Franco has joined the review team.

Keywords

MeSH

PICO

Population
Intervention
Comparison
Outcome

El uso y la enseñanza del modelo PICO están muy extendidos en el ámbito de la atención sanitaria basada en la evidencia para formular preguntas y estrategias de búsqueda y para caracterizar estudios o metanálisis clínicos. PICO son las siglas en inglés de cuatro posibles componentes de una pregunta de investigación: paciente, población o problema; intervención; comparación; desenlace (outcome).

Para saber más sobre el uso del modelo PICO, puede consultar el Manual Cochrane.

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

Updated study flow diagram, 20 June 2017

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.

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.

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.

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.

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.

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.

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).

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).

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.

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).

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).

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.

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.

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).

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
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
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
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
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
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