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High-carbohydrate, high-protein, low-fat versus low-carbohydrate, high-protein, high-fat enteral feeds for burns

  1. Bronwen Masters1,*,
  2. Shahram Aarabi2,
  3. Feroze Sidhwa3,
  4. Fiona Wood4

Editorial Group: Cochrane Injuries Group

Published Online: 18 JAN 2012

Assessed as up-to-date: 28 NOV 2011

DOI: 10.1002/14651858.CD006122.pub3


How to Cite

Masters B, Aarabi S, Sidhwa F, Wood F. High-carbohydrate, high-protein, low-fat versus low-carbohydrate, high-protein, high-fat enteral feeds for burns. Cochrane Database of Systematic Reviews 2012, Issue 1. Art. No.: CD006122. DOI: 10.1002/14651858.CD006122.pub3.

Author Information

  1. 1

    Sports Institute Northern Ireland, Newtownabbey, Northern Ireland, UK

  2. 2

    University of Washington, Department of Surgery, Seattle, Washington, USA

  3. 3

    Boston University Medical Center, Boston, Massachusetts, USA

  4. 4

    Royal Perth Hospital, Plastic Surgery, Perth, Western Australia, Australia

*Bronwen Masters, Sports Institute Northern Ireland, University of Ulster, Newtownabbey, Northern Ireland, BT37 0QB, UK. bronwen.masters@bigpond.com. bronwen.masters@aspetar.com.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 18 JAN 2012

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Background

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Differences between protocol and review
  16. Index terms

Nutritional support is critically important in patients with extensive burn injuries. In such patients, energy and protein requirements increase to approximately double the requirements of a healthy person. The introduction of "aggressive nutrition support" in burn patients in the early 1970s dramatically improved patient survival. A review from 1971 to 1975 (Alexander 1990) of patients with burns to greater than 50% of total body surface area (TBSA) provided with adequate nutrition showed an 80% drop in mortality due to septicaemia. This decrease in septicaemia was attributed to aggressive nutritional support (Alexander 1990). It is reported that the risk of death is markedly higher in patients who lose greater than one fourth of their body weight after burn injury (Herndon 2007).

Research suggests nutritional support in burn patients will reduce the severity of the hypermetabolic response, reduce catabolism and loss of muscle mass, improve and hasten wound healing, reduce rates of infection, improve integrity and function of the gut, and reduce hospital length of stay.

Inappropriate nutritional support may lead to adverse outcomes including fatty liver disease, decreased lean muscle mass, increased body fat mass, cardiopulmonary complications, and increased infectious complications. Since these discoveries, nutritional support in burns patients has been investigated. Research has been completed on many aspects of nutritional requirements in burn patients, including timing of feeding, optimal tube placement, vitamin and mineral supplementation, fish oil supplementation, and use of immune-modulating amino acids and macronutrients. Despite the large amount of published research, optimal feeding practices have not yet been delineated. Macronutrients (carbohydrate, fat and protein) make up the base of nutritional support. If these proportions are incorrect the benefits of micronutrients may well be lost.

 

Description of the condition

Patients with severe burns (second or third degree burns to greater than 10% of their total body surface area) often require aggressive nutritional support. The body's reaction to severe burns is a hypermetabolic response: greatly increased energy requirements, sustained release of catabolic hormones leading to muscle breakdown, and poor glycaemic control. Enteral feeding - controlled feeding of a prepared formula directly into the stomach or small intestine via a tube - is a mainstay of treatment for patients with severe burns (Herndon 2007).

 

Description of the intervention

This review explored the impact of macronutrient composition of enteral feeds (tube feeds into the stomach or intestine) on clinical outcomes. Parenteral nutrition (intravenous feeding) was not investigated.

Macronutrients are "macromolecules in plant and animal structures that can be digested, absorbed and utilised by other organisms as energy sources and as a substrate for the synthesis of the carbohydrates, fats, and proteins required to maintain cell and system integrity" (Escott-Stump 2004). Macronutrients of importance in humans are fat, carbohydrate and protein. In the healthy population it is recommended that at least 55% of energy comes from carbohydrate, less than 30% of energy comes from fat, and more than 15% of energy comes from protein.

Interventions for enteral feeding in burn patients can be split into two categories:

  1. high-carbohydrate, high-protein, low-fat enteral formula (high-carbohydrate enteral formula) providing at least 55% of total energy from carbohydrates, 20-25% of total energy from protein, and less than 25% of energy from fat; or
  2. low-carbohydrate, high-protein, high-fat enteral formula (high-fat enteral formula) providing less than 55% total energy from carbohydrates, 20-25% of total energy from protein, and at least 25% of total energy from fat.

Interventions may provide varying quantities of fish oils as a fat source. At least one study has linked fish oil supplementation to decreased infectious complications, reduced length of hospital stay, reduced incidence of diarrhoea, and decreased loss of muscle mass in burn patients (Gottschlich 1990b).

Enteral feeds are usually commenced within 24 hours of admission for severe burn injuries. The feeding tube may supply the stomach (as in orogastric, nasogastric, or percutaneous endoscopic gastrostomy tubes) or the small intestine (as in nasoduodenal, nasojejunal, or percutaneous endoscopic jejunostomy tubes), depending on various clinical factors and physician preference.

 

How the intervention might work

The ratio of macronutrients in enteral feeds may influence clinical outcomes in burn patients in two ways:

 

1. Hypermetabolic response

The hypermetabolic response to significant burn injury increases energy and protein requirements to approximately twice basal requirements and leads to significant loss of lean mass and total weight loss. Furthermore, the hypermetabolic response alters the way the body metabolises and utilises macronutrients. Breakdown of muscle tissue and fat stores is increased, with the breakdown products fuelling increased hepatic gluconeogenesis. This response cannot be completely stopped with currently available treatments, but it may be possible to reduce the severity of protein breakdown.

Variations in the macronutrient composition of enteral feeds may limit the detrimental effects of the hypermetabolic response. For example, it is suggested that a high-carbohydrate energy source may increase blood insulin levels, thereby reducing the hormonal stimulus for muscle protein catabolism.

 

2. Gastrointestinal (GI) tolerance

Burn patients on enteral feeds often experience nausea, vomiting, diarrhoea and/or constipation, and often do not absorb dietary macronutrients as well as non-burn patients. Therefore, it is important to maximise GI tolerance in order to maximize the possibility of a patient receiving and absorbing required levels of nutrition.

It is possible that different macronutrient compositions will improve GI tolerance and thereby improve nutritional status and clinical outcomes. It is known that carbohydrates are digested more quickly than fats and proteins, and therefore it is hypothesised that a high-carbohydrate enteral feeding regimen is more quickly absorbed than a high-fat enteral feeding regimen. Decreases in absorption time may improve GI tolerance in burn patients.

A study assessing diarrhoea in burns patients showed that using a lower fat feed (less than 20% of caloric intake) reduced the frequency of diarrhoea in these patients (Gottschlich 1988). However, it remains unclear what combination of macronutrients the GI tract will tolerate best.

 

Why it is important to do this review

No systematic review has been completed investigating enteral feeding in burns patients and the role of fat and carbohydrates in optimising the management of a burn injury. This review will add to an overall understanding about the role of carbohydrates and fats in nutrition support in burn patients. The optimal combination of enteral macronutrients should help to optimise clinical outcomes in these patients by reducing the hypermetabolic response and muscle protein breakdown, and conversely by promoting anabolism and improved wound healing. Furthermore, optimization of enteral macronutrient proportions should improve GI tolerance, minimizing diarrhoea, constipation, nausea and vomiting, and promoting gut health generally. Assessing optimal macronutrient proportions may allow care providers to appropriately weigh patient factors (e.g. hyperglycaemia) when deciding whether or not to manipulate the macronutrient proportions in a patient's enteral formula.

This review seeks to aid in developing an evidence-based approach to the medico-nutritional management of burn patients, potentially justifying clinical recommendations and informing future research efforts.

 

Objectives

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Differences between protocol and review
  16. Index terms

To examine the evidence of improved clinical outcomes in burn patients treated with high-carbohydrate enteral feeds compared with those treated with high-fat enteral feeds.

 

Methods

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Differences between protocol and review
  16. Index terms
 

Criteria for considering studies for this review

 

Types of studies

We included randomized controlled trials (RCTs) comparing high-carbohydrate enteral feeding to high-fat enteral feeding in severely burned patients.

 

Types of participants

Patients must have burns to at least 10% of their total body surface area (TBSA) and have received enteral nutrition. Trials involving patients with any agent of burn injury (thermal, chemical, or electrical) and of any age were eligible. No criteria were set for participant characteristics (age, gender, etc.).

 

Types of interventions

Enteral tube feeding with a high-carbohydrate feeding regimen versus enteral tube feeding with a high-fat feeding regimen was considered. All mechanisms of enteral feeding (gastric, duodenal, and jejunal feeding) were considered. The source of macronutrients was not considered in this review.

Macronutrient composition was defined as follows:

  1. high-carbohydrate, high-protein, low-fat enteral formula (high-carbohydrate enteral formula): at least 55% of energy from carbohydrates, 20-25% of energy from protein, and less than 25% of energy from fat;
  2. low-carbohydrate, high-protein, high-fat feed (high-fat enteral formula): less than 55% of energy from carbohydrates, 20-25% of energy from protein, and at least 25% of energy from fat.

 

Types of outcome measures

Outcomes were divided into primary and secondary outcomes.

 

Primary outcomes

  • Mortality.
  • Incidence of sepsis or pneumonia.
  • Time to healing.
  • Number of days on ventilator.

 

Secondary outcomes

  • Glycaemic control.
  • Insulin requirements.
  • Weight change.
  • Protein turnover via tagged amino acid studies.
  • Nitrogen balance.

 

Search methods for identification of studies

The search for trials was not restricted by date, language or publication status.

 

Electronic searches

We searched the following electronic databases:

  • Cochrane Injuries Group Specialised Register (searched 28 Nov 2011),
  • Cochrane Central Register of Controlled Trials (The Cochrane Library 2011, Issue 4),
  • MEDLINE (Ovid)1950 to Nov (Week 3) 2011,
  • EMBASE (Ovid) (1980 to Nov (week 46)  2011),
  • ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED) (1970 to Nov 2011),
  • ISI Web of Science: Conference Proceedings Citation Index-Science (CPCI-S) (1990 to Nov 2011),
  • PubMed [www.ncbi.nlm.nih.gov/sites/entrez/] (Searched 28 Nov 2011).

All search strategies are reported in full in Appendix 1.

 

Searching other resources

We handsearched the following conference abstracts:

  • American Burn Association meetings: 1997 to 2008;
  • Dietitians Association of Australia meetings: 1990 to 2010;
  • Burns meeting abstracts: 2003 to 2010;
  • Journal of Burn Care and Research: 2003 to 2010;
  • Journal of Human Nutrition and Dietetics: 2003 to 2010;
  • Journal of the American Dietetic Association: 2003 to 2010.

We searched the reference lists of previously published reviews and other relevant material for further eligible studies.

 

Data collection and analysis

The Injuries Group Trials Search Co-ordinator ran the searches and collated the results using bibliographic software (EndNote X3 bld 5276), before passing them on to two authors (SA, FS) who independently screened the search results for eligibility.

 

Selection of studies

We obtained the full text of all relevant records and independently assessed whether each one met the pre-defined eligibility criteria. No disputes arose (kappa = 1), and no duplicate studies were found. Figure 1 illustrates the study retrieval and selection process.

 FigureFigure 1. Study retrieval and selection process

 

Data extraction and management

Data were extracted independently by two authors (BM, FS). A standard form created by one author (SA) was used to extract the following:

  • study characteristics: source, authors, time period of trial, date of publication, population studied;
  • study design details: eligibility criteria, study type and allocation, method of randomization, dropouts/withdrawals, interventions, exclusions;
  • participants: age range, gender, care setting, total number, location, % TBSA burned;
  • risk of bias: sequence generation, allocation concealment, blinding, incomplete outcome data addressed, selective reporting, other biases;
  • sample size: number of patients in each arm of trial;
  • intervention details: % calories from non-enteral sources, macronutrient composition and source, other supplements, total kcal/kg/day, timing and duration of each intervention;
  • outcome measures: types of outcomes measured, time points collected, outcomes and time points reported, outcome definition, diagnostic criteria, units of measurement, missing data, summary data, effect estimate, 95% confidence interval (CI);
  • analysis: description of analysis employed;
  • miscellaneous: funding sources, authors' conclusions, references found to other relevant studies.

These data were cross-checked for accuracy. No disputes arose. Data were entered into the Cochrane Collaboration's Review Manager software, version 5 (Review Manager).

 

Assessment of risk of bias in included studies

Two authors independently assessed study quality (BM, FS).

The recommended approach for assessing risk of bias in studies included in systematic reviews from the Cochrane Handbook (Higgins 2011) was used. Briefly, a two-part tool was used which addressed six specific domains for assessment of bias (listed below). Each domain included one or more specific entries in a "risk of bias" table. Within each entry, the first part of the tool involved describing what was reported to have happened in the study. The second part of the tool involved assigning a judgement relating to the risk of bias for that entry. This was achieved by answering a pre-specified question about the adequacy of the study in relation to the entry, such that a judgement of "yes" indicated a low risk of bias, "no" indicated a high risk of bias, and "unclear" indicated unclear or unknown risk of bias.

The categories were as follows:

  1. Was the allocation sequence adequately generated?
  2. Was allocation adequately concealed?
  3. Was knowledge of the allocated interventions adequately concealed during the study?
  4. Were incomplete outcome data adequately addressed?
  5. Are reports of the study free of suggestion of selective outcome reporting?
  6. Was the study apparently free of any other problems that could put it at a risk of bias, for example, patient, investigator or data analysis problems?

 

Data synthesis

All data were entered into Review Manager software, version 5. A random-effects model was used for all comparisons.

For ordinal and nominal variables (incidence of pneumonia and mortality), both individual and pooled statistics were expressed as odds ratios (OR) with 95% confidence intervals (CI). For continuous variables (days on ventilator), mean difference with 95% CI was reported. Statistical significance was defined as a P value ≤ 0.05.

An intention-to-treat analysis could not be performed, as only one study reported data in an intention-to-treat fashion (Gottschlich 1990a), and the other study's author could not be contacted (Garrel 1995).

 

Results

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Differences between protocol and review
  16. Index terms
 

Description of studies

See: Characteristics of included studies; Characteristics of excluded studies.

We found 1121 records through the searches. Based on title and abstract screening we excluded 1116 and examined 5 studies in further detail by obtaining full text copies. We excluded three of the studies (Hart 2001; Saffle 1997; Serog 1983) because their enteral feeding regimens did not meet the study requirements. Two studies (Garrel 1995; Gottschlich 1990a) were eligible for inclusion in this systematic review. We had uniform inter-observer agreement on study inclusion eligibility (kappa = 1); no disagreements arose requiring discussion or a mediator. See Figure 2 for the results of the bias assessment tool for the two included studies.

 FigureFigure 2. Methodological quality summary: review authors' judgements about each methodological quality item for each included study.

Gottschlich 1990a reported a randomized controlled trial, initially enrolling 50 patients aged three years or older with thermal injury to greater than 10% TBSA. All patients were admitted to the Cincinnati Shriners Burns Institute or Cincinnati University Hospital within five days of burn between 6 April 1986 and 20 May 1988. No patient exclusion criteria were given. Patients were followed until death or discharge from the hospital. Patients were randomized to one of three treatment groups using "a random number table stratified for age, institution and burn size". The three treatment groups were group 1, a high-fat feed group; group 2, which received a high-carbohydrate "modular tube feed" designed by the study's authors; and group 3, another high-fat feed group. All patients enrolled in the study received vitamins A and C and zinc supplementation enterally. "Parenteral nutrition was reserved for those who could not be given adequate nutritional support enterally. It was used for as short a time as possible without compromising the adequacy of nutritional support." The number of patients requiring total parenteral nutrition (TPN) and the mean number of days on TPN was not statistically significantly different between the three intervention groups.

The primary aim of this study was to "evaluate and differentiate the effects of three nutrition support regimens with one treatment group randomized to receive the new modular tube feeding." Outcomes assessed included diarrhoea (cumulative incidence as a percentage, total days with, and mean days with), constipation (number of patients experiencing, and total days with), glycaemic control (mean days requiring exogenous insulin, and mean insulin days), number of patients with bacteraemia, number of patients with wound infection, number of patients with pneumonia, mean days on ventilator, discharge weight as a percentage of pre-burn weight, and mortality. No data were available for sepsis score, time to healing, insulin requirements, protein turnover, nitrogen balance, or nutritional status serum markers.

Of the 50 patients initially enrolled in the study, 10 died before discharge. These patients' data were included in all measures other than hospital length of stay (Gottschlich correspondence), thus, this study's data were reported on an intention-to-treat basis. The study authors found no statistically significant differences in glycaemic control, days on ventilator, mortality, cumulative incidence of pneumonia or sepsis, or discharge weight as a percentage of pre-burn weight using analysis of variance between the three groups. No analysis combining groups 1 and 3 into 'high-fat' and comparing this combined group with group 2 as 'high-carbohydrate' was reported.

Garrel 1995 reported a randomized controlled trial, initially enrolling 43 adult patients with thermal injury to greater than 20% TBSA, excluding first-degree burns. All patients were admitted within 24 hours of injury between September 1990 and September 1994. Patient exclusion criteria included people aged over 65, body mass index greater than 30, pre-existing diabetes or chronic visceral insufficiency, and chronic use of either alcohol or cocaine. Patients were followed for 30 days. Patients were randomized to one of three treatment groups using a random number table. One treatment group received a high-fat enteral feeding formula, and was treated as the control group; the second group received a high-carbohydrate enteral feeding formula without omega-3 fatty acid supplementation; the third group received a high-carbohydrate enteral feeding formula with omega-3 fatty acid supplementation. All treatment groups received parenteral nutrition in addition to enteral feeding. Energy delivered through parenteral nutrition was not statistically significantly different between the three intervention groups, nor was it statistically significantly different in a combined analysis of the two high-carbohydrate groups versus the high-fat (control) group.

The primary aim of the study was to assess the effects of high-carbohydrate enteral nutritional support with and without omega-3 fatty acid supplementation on clinical outcomes, protein sparing and several serum biomarkers, and to compare both of these enteral feeding regimens with the high-fat control group. Reported end-points included mortality, sepsis score, incidence of pneumonia, exogenous insulin requirements, and hospital length of stay. No data were available for number of days on ventilator, glycaemic control, weight change, protein turnover, nitrogen balance, nutritional status or bowel habits.

 

Risk of bias in included studies

Assessment of bias for the RCTs was completed using the Cochrane Collaboration's 'Risk of Bias' tool (Higgins 2011). This two part tool used pre-specified questions to assess the methodological quality of the study. A judgement of 'yes' indicates low risk of bias, 'no' high risk of bias and 'unclear' if a judgement could not be made.

 

Random sequence generation (selection bias)

The randomization sequence was generated using a random number table in both studies.

 

Allocation

There was good allocation concealment in the Garrel 1995 study. Allocation concealment was not reported in the Gottschlich 1990a study.

 

Blinding

Both studies blinded nursing and medical staff. Garrel 1995 notified the investigator of patients' randomization groups only after allocation. Dr. Gottschlich reports via correspondence that tube feeds were delivered in cartons labelled only as "research tube feeding", while caregivers and patients were given no information on which feed they actually received (Gottschlich correspondence).

 

Incomplete outcome data

Both studies were inpatient studies reporting outcome data collected as part of routine care. As caregivers were blinded in both studies, authors consider there is a low risk of bias. However, Garrel 1995 excluded patients who died in the first three weeks into the study and reported "available case" data. See risk of bias table for further information.

 

Selective reporting

No study protocol was published for either study, and so reporting bias is unknown.

 

Other potential sources of bias

Of the 43 patients initially admitted to the Garrel 1995 study, six died before the end of the third week of admission. These patients were excluded from the analysis, and thus this study's data were reported on an available case basis, not an intention-to-treat basis. Thirty-seven patients were included in the reported data. Two patients who died after completion of the study were included in the reported data.

Based on these strengths and weaknesses we judge Gottschlich 1990a to have an overall moderate risk of bias and Garrel 1995 to have an overall high risk of bias.

 

Effects of interventions

Garrel 1995 reported available case data for 37 patients with burn injury. Mortality and cumulative incidence of pneumonia were reported as dichotomous end-points, while sepsis score, daily insulin requirements, and hospital length of stay were reported as continuous or ordinal end-points. The study authors concluded that compared to the high-fat group, the high-carbohydrate groups had a lower 30-day cumulative incidence of pneumonia, and required less exogenous insulin. Differences in mortality, sepsis score and length of care did not reach statistical significance.

Gottschlich 1990a reported intention-to-treat data for 50 patients with burn injury. Mortality, length of stay per percentage burn, cumulative incidence of pneumonia, cumulative incidence of sepsis, and cumulative incidence of constipation were reported as dichotomous end-points. Average days on ventilator, discharge weight as a percentage of pre-burn weight, mean diarrhoeal days, and mean days requiring exogenous insulin were reported as continuous end-points. This study reported statically significant reductions in wound infection (P < 0.03) and length of stay (P < 0.02) with low fat enteral feeds. It also identified trends to decreased diarrhoeal days and improved glucose tolerance although these were not statistically significant.

Common outcomes between the two studies were mortality and cumulative incidence of pneumonia. Insulin requirements were reported in both papers, but Garrel 1995 did not report standard errors or confidence intervals, and attempts to contact the study authors were unsuccessful. In meta-analysis, use of a high-carbohydrate enteral feeding regimen was associated with a mortality OR of 0.36 (95% CI 0.11 to 1.15, P = 0.08) ( Analysis 1.1), and a cumulative incidence of pneumonia OR of 0.12 (95% CI 0.04 to 0.39, P = 0.004) ( Analysis 1.2), compared to a high-fat enteral feeding regimen. The mortality OR did not reach statistical significance, while the cumulative incidence of pneumonia OR did reach statistical significance.

Average number of days on a ventilator was reported in Gottschlich 1990a only. Combining groups 1 and 3 from this study to form a high-fat group and comparing to group 2 as a high-carbohydrate group, use of a high-carbohydrate enteral feeding regimen was associated with a days on a ventilator mean difference (MD) of -3.30 (95% CI -5.80 to -0.80) ( Analysis 1.3). This result reached statistical significance (P value = 0.01). Note that these results are not from a meta-analysis of studies, but rather an analysis combining Gottschlich 1990a's three groups into two.

No meta-analysis could be performed on the remaining outcomes data due to lack of similar outcomes reported between the two available studies.

 

Discussion

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Differences between protocol and review
  16. Index terms

This systematic review of the effect of high-carbohydrate, high-protein, low-fat enteral feeding (high-carbohydrate enteral feeding) regimens versus low-carbohydrate, high-protein, high-fat enteral feeding (high-fat enteral feeding) regimens in patients with significant burn injuries includes two RCTs, one judged to be of moderate risk of bias, and the other as high. Each study had a small number of participants.

Meta-analysis of the two studies indicates the risk of pneumonia is lower in burn patients receiving a high-carbohydrate enteral feeding regimen than in those receiving a high-fat enteral feeding regimen. No conclusions could be drawn about the risk of death in patients receiving the different feeding regimens.

There may be any number of molecular and/or cellular mechanisms to explain the decreased risk of pneumonia observed in patients receiving a high-carbohydrate enteral feeding regimen compared to those receiving a high-fat enteral feeding regimen. Most immune system cells are obligate glucose consumers (Deitch 1995), and research suggests rates of glycolysis may nearly double in severely burned patients (Gore 2001; Wolfe 1979). High-carbohydrate enteral feeding regimens may supply glucose required by highly active immune system cells. Likewise, inadequate provision of dietary glucose may limit intracellular availability and subsequently impair immune system function. It is well established that chronic hyperglycaemia inhibits wound healing and increases the risk of infectious complications in the intensive care setting (Herndon 2007; Marino 2007). However, severe burn patients develop a hypermetabolic response and are monitored closely in an intensive care setting, thus they are unlikely to become hyperglycaemic even in the setting of a high-carbohydrate diet. Conversely, high dietary fat intake may increase the risk of pneumonia by increasing the production of pro-inflammatory cytokines and negatively effecting prostaglandin metabolism (Bernier 1998; Erridge 2007).

It has been suggested that high-fat formulas are beneficial for ventilated burn patients because they may decrease CO2 production (al Saady 1989) and length of time requiring mechanical ventilation (van de Berg 1994). However, combining the three study groups reported in Gottschlich 1990a into two groups - one high-carbohydrate enteral feeding group and one high-fat enteral feeding group - indicates that patients given a high-carbohydrate enteral feeding regimen spend fewer mean days mechanically ventilated than patients given a high-fat enteral feeding regimen. (Note again: this observed effect is from one relatively small study judged to have a moderate risk of bias.) If this observed effect is a true effect, then a high-carbohydrate enteral feeding regimen reduces the average time burn patients are exposed to one of the most important risk factors for developing pneumonia in the intensive care setting (Herndon 2007; Marino 2007). The question then is: Why do patients given a high-carbohydrate enteral feeding regimen spend less time on average undergoing mechanical ventilation than those given a high-fat enteral feeding regimen? Indeed, the answer may be because they are less likely to develop pneumonia and thus to require mechanical ventilation in the setting of respiratory failure.

Much remains unknown about the cellular and molecular effects of dietary carbohydrate and fat intake on the human body. Further research, particularly into the effects of dietary macronutrients on the acute phase response to injury, is essential to further our understanding of the role dietary macronutrients play in the treatment of severely burned patients, and of trauma patients generally.

 

Authors' conclusions

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Differences between protocol and review
  16. Index terms

 

Implications for practice

Based on the currently available evidence, consisting of two relatively small studies (one with moderate risk of bias and the other with a high risk of bias), no firm conclusion can be made. There may be a possible clinical benefit to high-carbohydrate enteral feeds compared with high-fat enteral feeds in the treatment of burn injuries: a reduced risk of pneumonia. The molecular and cellular mechanisms by which this benefit may accrue remain unclear.

Based on the available evidence, one relatively small study with a moderate risk of bias, patients receiving high-carbohydrate feeds may spend less time undergoing mechanical ventilation than patients receiving a high-fat enteral feeding regimen. Again, why this may be the case is unclear.

While this review presents the currently available evidence, definitive clinical guidelines on the optimal macronutrient composition of enteral feeds in severely burned patients cannot be formulated without further research.

 
Implications for research

Further research is needed in order to determine the proportion of macronutrients in enteral feeding regimens that will optimize patient outcomes following severe burn injuries. Large, well-designed randomized controlled trials of burn patients would most effectively establish optimal enteral feeding practices. Animal and human research utilizing clinical outcomes as well as various biomarkers may add to our understanding of why high-carbohydrate enteral feeding regimens appear to be more beneficial to burn patients when compared to high-fat enteral feeding regimens. Continued research into the cellular and molecular effects of dietary fats and carbohydrates on the acute phase response to injury may help guide clinical research.

 

Acknowledgements

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Differences between protocol and review
  16. Index terms

We would like to acknowledge the study authors whom we contacted for more information, the enteral feed manufacturers who provided information on the existence of ongoing trials, and to the staff at the Cochrane Injuries Group, specifically Karen Blackhall and Emma Sydenham for their guidance and support. Li Peng and Jane Tuckerman contributed to the protocol for this review and Taixiang Wu at the Chinese Cochrane Centre located and translated Chinese-language studies. Annette Kaufman at the National Cancer Institute and Alexandra Soroceanu at Dalhousie University assisted with searching conference abstracts.

 

Data and analyses

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Differences between protocol and review
  16. Index terms
Download statistical data

 
Comparison 1. High-carbohydrate vs high-fat enteral feeding

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Mortality at final follow-up290Odds Ratio (M-H, Random, 95% CI)0.36 [0.11, 1.15]

 2 Risk of pneumonia287Odds Ratio (M-H, Random, 95% CI)0.12 [0.04, 0.39]

 3 Days on ventilator1Mean Difference (IV, Random, 95% CI)Subtotals only

 

Appendices

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Differences between protocol and review
  16. Index terms
 

Appendix 1. Search strategy

Cochrane Injuries Group Specialised Register (searched 28 Nov 2011)
1. (feed* or fed or nutrition* or nourish*) AND (enteral or enteric or gastric or gastro* or intub* or tube*)
2. (macronutrient* or carbohydrate* or starch* or glycogen* or polysaccharide* or monosaccharide* or glucose* or protein* or amino acid* or fat* or lipid*) AND (feed* or fed or nutrition* or nourish*)
3. (enteral or enteric or gastric or gastro* or intub* or tube*) AND (feed* or nutrition*)
4. (intub* or tube*) AND (feed* or gastrointest*)
5. 1 OR 2 OR 3 OR 4
6. Burn*
7. 5 and 6

Cochrane Central Register of Controlled Trials (The Cochrane Library 2011, Issue 4)
#1 MeSH descriptor Carbohydrates explode all trees
#2 MeSH descriptor Dietary Carbohydrates explode all trees
#3 MeSH descriptor Glycogen explode all trees
#4 MeSH descriptor Polysaccharides explode all trees
#5 MeSH descriptor Monosaccharides explode all trees
#6 MeSH descriptor Glucose explode all trees
#7 MeSH descriptor Amino Acids explode all trees
#8 MeSH descriptor Amino Acids, Essential explode all trees
#9 MeSH descriptor Fats explode all trees
#10 MeSH descriptor Lipids explode all trees
#11 MeSH descriptor Starch explode all trees
#12 (#1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10 OR #11)
#13 ((feed* or fed or nutrition* or nourish*) near (enteral or enteric or gastric or gastro* or intub* or tube*))
#14 (#12 AND #13)
#15 MeSH descriptor Enteral Nutrition explode all trees
#16 MeSH descriptor Intubation, Gastrointestinal explode all trees
#17 (macronutrient* or carbohydrate* or starch* or glycogen* or polysaccharide* or monosaccharide* or glucose* or protein* or amino acid* or fat* or lipid*) AND ((feed* or fed or nutrition* or nourish*) near (enteral or enteric or gastric or gastro* or intub* or tube*))
#18 (enteral or enteric or gastric) near (feed* or nutrition*)
#19 (intub* or tube*) near (feed* or gastrointest*)
#20 (#14 OR #15 OR #16 OR #17 OR #18 OR #19)
#21 MeSH descriptor Burns explode all trees
#22 burn*
#23 (#21 OR #22)
#24 (#20 AND #23)

MEDLINE (Ovid)1950 to Nov (Week 3) 2011
1. exp carbohydrates/
2. exp dietary carbohydrates/
3. exp glycogen/
4. exp polysaccharides/
5. exp monosaccharides/
6. exp glucose/
7. exp amino acids/
8. exp amino acids essential/
9. exp fats/
10. exp lipids/
11. exp starch/
12. or/1-11
13. ((feed$ or fed or nutrition$ or nourish$) and (enteral or enteric or gastric or gastro$ or intub$ or tube$)).ab,ti.
14. 12 and 13
15. exp enteral nutrition/
16. exp intubation gastrointestinal/
17. (macronutrient$ or carbohydrate$ or starch$ or glycogen$ or polysaccharide$ or monosaccharide$ or glucose$ or protein$ or amino acid$ or fat$ or lipid$).ab,ti.
18. ((enteral or enteric or gastric) adj3 (feed$ or nutrition$)).ab,ti.
19. ((intub$ or tube$) adj3 (feed$ or gastrointest$)).ab,ti.
20. 14 or 15 or 16 or 17 or 18 or 19
21. exp burns/
22. burn$.ab,ti.
23. 21 or 22
24. 20 and 23
25. randomi?ed.ab,ti.
26. randomized controlled trial.pt.
27. controlled clinical trial.pt.
28. placebo.ab.
29. clinical trials as topic.sh.
30. randomly.ab.
31. trial.ti.
32. 25 or 26 or 27 or 28 or 29 or 30 or 31
33. (animals not (humans and animals)).sh.
34. 32 not 33
35. 24 and 34

EMBASE (Ovid) 1980 to week 46, Nov 2011
1. exp Carbohydrate/
2. exp carbohydrate diet/
3. exp Monosaccharide/
4. exp Glycogen/
5. exp Polysaccharide/
6. exp Glucose/
7. exp Amino Acid/
8. exp Essential Amino Acid/
9. exp Fat/
10. exp Lipid/
11. exp Starch/
12. or/1-11
13. ((feed$ or fed or nutrition$ or nourish$) and (enteral or enteric or gastric or gastro$ or intub$ or tube$)).ab,ti.
14. 12 and 13
15. exp enteral nutrition/
16. exp intubation gastrointestinal/
17. (macronutrient$ or carbohydrate$ or starch$ or glycogen$ or polysaccharide$ or monosaccharide$ or glucose$ or protein$ or amino acid$ or fat$ or lipid$).ab,ti.
18. ((enteral or enteric or gastric) adj3 (feed$ or nutrition$)).ab,ti.
19. ((intub$ or tube$) adj3 (feed$ or gastrointest$)).ab,ti.
20. 14 or 15 or 16 or 17 or 18 or 19
21. exp enteric feeding/
22. exp nose feeding/
23. exp tube feeding/
24. exp digestive tract intubation/
25. exp duodenum intubation/
26. exp esophagus intubation/
27. exp stomach intubation/
28. or/20-27
29. exp Burn/
30. burn$.ab,ti.
31. 29 or 30
32. 28 and 31
33. exp Randomized Controlled Trial/
34. exp controlled clinical trial/
35. randomi?ed.ab,ti.
36. placebo.ab.
37. *Clinical Trial/
38. randomly.ab.
39. trial.ti.
40. 33 or 34 or 35 or 36 or 37 or 38 or 39
41. exp animal/ not (exp human/ and exp animal/)
42. 40 not 41
43. 32 and 42

ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED) (1970 to Nov 2011);
ISI Web of Science: Conference Proceedings Citation Index-Science (CPCI-S) (1990 to Nov 2011)
1. (feed* or fed or nutrition* or nourish*) NEAR/3 (enteral or enteric or gastric or gastro* or intub* or tube*)
2. (enteral or enteric or gastric or gastro* or intub* or tube*) NEAR/3 (feed* or nutrition*)
3. (macronutrient* or carbohydrate* or starch* or glycogen* or polysaccharide* or monosaccharide* or glucose* or protein* or amino acid* or fat* or lipid*) NEAR/3 (feed* or fed or nutrition* or nourish*)
4. #1 or #2 or #3
5. Burn*
6. 4 AND 5
7. Topic=((singl* OR doubl* OR trebl* OR tripl*) NEAR/3 (blind* OR mask*)) OR Topic=((clinical OR control* OR placebo OR random*) NEAR/3 (trial* or group* or study or studies or placebo or controlled)) NOT Title=(Animal* or rat or rats or rodent* or mouse or mice or murine or dog or dogs or canine* or cat or cats or feline* or rabbit or rabbits or pig or pigs or porcine or swine or sheep or ovine* or guinea pig*)
8. 6 and 7

PubMed [www.ncbi.nlm.nih.gov/sites/entrez/] (Searched 28 Nov 2011)
1. "Enteral Nutrition"[Mesh] OR "Intubation, Gastrointestinal"[Mesh]
2. (enteral or enteric or gastric) and (feed* or nutrition*)
3. (macronutrient* or carbohydrate* or starch* or glycogen* or polysaccharide* or monosaccharide* or glucose or protein or amino acid* or fat or fats or lipid or lipids) AND ((feed* or fed or nutrition* or nourish*) and (enteral or enteric or gastric or gastrointestinal* or intub* or tube or tubes or tubal*))
4. 1 or 2 or 3
5. burn*
6. 4 and 5
7. ((randomized controlled trial[pt] OR controlled clinical trial[pt]) OR (randomized OR randomised OR randomly OR placebo[tiab]) OR (trial[ti]) OR ("Clinical Trials as Topic"[MeSH Major Topic])) NOT (("Animals"[Mesh]) NOT ("Humans"[Mesh] AND "Animals"[Mesh]))
8. 6 and 7

 

What's new

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Differences between protocol and review
  16. Index terms

Last assessed as up-to-date: 28 November 2011.


DateEventDescription

18 January 2012AmendedThe date next expected has been corrected to January 2014.



 

History

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Differences between protocol and review
  16. Index terms

Protocol first published: Issue 3, 2006
Review first published: Issue 1, 2012

 

Contributions of authors

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Differences between protocol and review
  16. Index terms

Masters B: Drafting of protocol and review, data extraction, general advice on review and clinical perspective, editing and incorporation of reviewer comments.

Aarabi S: Drafting of review, searching and selection of studies, creation of data extraction form, data analysis, data interpretation, drafting of review, editing.

Sidhwa F: Drafting of review, searching and selection of studies, contact and correspondence with authors, contact and correspondence with formula manufacturers, data extraction, data analysis, data interpretation, incorporation of reviewer comments and revision of review, recording of changes made according to reviewer comments, editing.

Wood F: Drafting of protocol, general advice on review and clinical perspective.

 

Declarations of interest

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Differences between protocol and review
  16. Index terms

None known.

 

Differences between protocol and review

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Differences between protocol and review
  16. Index terms

Cochrane guidance on the assessment of the risk of bias for included studies has changed since publication of the protocol on which this review was based. The instructions from the latest version of the Cochrane Handbook (Higgins 2011) were used as the basis for this review. Some grey literature sources mentioned in the protocol were excluded and others were included based on availability. Comparative data on time to healing, weight, protein turnover, nutritional status markers and bowel habits were not included in the final review as each was reported in only one of the two studies included in the review.

The protocol stated study participants would be limited to "patients with burns to 15% TBSA or greater...". This review includes patients with burns to 10% TBSA or greater. This was done so that Gottschlich 1990a could be included, and because no widely recognized definition of "severe" burn injury exists.

The protocol stated trials "allowing greater than 50% of intake from alternative sources of nutrition" and trials "that provide significant volumes of dextrose infusions in conjunction with low carbohydrate feeds" would be excluded. This exclusion criteria was modified for this review, as macronutrients provided through parenteral feeding did not differ between groups and authors were confident any feeding effects would be related to enteral feeds.

References

References to studies included in this review

  1. Top of page
  2. AbstractRésumé scientifiqueResumo
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Differences between protocol and review
  17. Characteristics of studies
  18. References to studies included in this review
  19. References to studies excluded from this review
  20. Additional references
Garrel 1995 {published data only}
  • Garrel DR, Razi M, Lariviere F, Jobin N, Naman N, Emptoz-Bonneton A, et al. Improved clinical status and length of care with low-fat nutrition support in burn patients. Journal of Parenteral and Enteral Nutrition 1995;19(6):482-91.
Gottschlich 1990a {published data only}
  • Gottschlich M, Jenkins M, Warden G, Baumer T, Havens P, Snook J, et al. Differential effects of three enteral dietary regimens on selected outcome variables in burn patients. Journal of Parenteral and Enteral Nutrition 1990;14(3):225-36.

References to studies excluded from this review

  1. Top of page
  2. AbstractRésumé scientifiqueResumo
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Differences between protocol and review
  17. Characteristics of studies
  18. References to studies included in this review
  19. References to studies excluded from this review
  20. Additional references
Hart 2001 {published data only}
Saffle 1997 {published data only}
Serog 1983 {published data only}
  • Serog P, Baigts F, Apfelbaum M, Guilbaud J, Chauvin B, Pecqueur ML. Energy and nitrogen balances in 24 severely burned patients receiving 4 isocaloric diets of about 10 MJ/m2/day (2392 Kcalories/m2/day). Burns 1983;9(6):422-7.

Additional references

  1. Top of page
  2. AbstractRésumé scientifiqueResumo
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Differences between protocol and review
  17. Characteristics of studies
  18. References to studies included in this review
  19. References to studies excluded from this review
  20. Additional references
al Saady 1989
  • al-Saady NM, Blackmore CM, Bennett ED. High fat, low carbohydrate, enteral feeding lowers PaCO2 and reduces the period of ventilation in artificially ventilated patients. Intensive Care Medicine 1989;15(5):290-5.
Alexander 1990
Bernier 1998
  • Bernier J, Jobin N, Emptoz-Bonneton A, Pugeat MM, Garrel DR. Decreased corticosteroid-binding globulin in burns patients: a relationship with interleukin-6 and fat in nutritional support. Critical Care Medicine 1998;26(3):452-60.
Deitch 1995
Erridge 2007
  • Erridge C, Attina T, Spickett CM, Webb DJ. A high-fat meal induces low-grade endotoxemia: evidence of a novel mechanism of postprandial inflammation. American Journal of Clinical Nutrition 2007;86(5):1286-92.
Escott-Stump 2004
  • Mahan LK, Escott-Stump S. Krause's Food, Nutrition, & Diet Therapy. 11th Edition. Philadelphia, PA: W.B. Saunders, 2004.
Gore 2001
  • Gore DC, Chinkes D, Heggers J, Herndon DN, Wolf SE, Desai M. Association of hyperglycemia with increased mortality after severe burn injury. Journal of Trauma-Injury Infection & Critical Care 2001;51(3):540-4.
Gottschlich 1988
  • Gottschlich MM, Warden GD, Michel M, Havens P, Kopcha R, Jenkins M, et al. Diarrhea in tube-fed burn patients: incidence, etiology, nutritional impact, and prevention. Journal of Parenteral and Enteral Nutrition 1988;12(4):338-45.
Gottschlich 1990b
  • Gottschlich M, Alexander J, Bower R. Enteral nutrition in patients with burns or trauma. In: Rombeau JL, Caldwell MD editor(s). Clinical Nutrition: Enteral and Tube Feeding. 2nd Edition. Philadelphia, PA: W.B. Saunders, 1990.
Gottschlich correspondence
  • Gottschlich MM. Email correspondence (mgottschlich@shrinenet.org) 21 January 2011 - 8 March 2011.
Herndon 2007
  • Herndon DN. Total Burn Care. 3rd Edition. Edinburgh, UK: Saunders Elsevier, 2007.
Higgins 2011
  • Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane-handbook.org.
Marino 2007
  • Marino PL. The ICU Book. 3rd Edition. Philadelphia, PA: Lippincott Williams & Wilkins, 2007.
Review Manager
  • The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). 5.1. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2011.
van de Berg 1994
Wolfe 1979