Introduction

The metabolic effects of burns are among the most extreme of all critically ill patients.1 Burn injuries cause an associated physiological stress that is manifested in hypermetabolism, protein catabolism and weight loss.1 The degree of hypermetabolism is roughly proportional to the extent of the injury.2 Nutrition support has been identified to have many benefits for patients with burns, including preservation of lean body mass, promotion of wound healing, reduction of gut mucosal permeability, enhancement of immunologic defences,3,4 reduction in Curling's ulcers, increased insulin levels, reduced catecholamine levels and reduced mortality.5

Literature suggests that underfeeding patients with burn injuries can negatively impact patient outcomes such as increased length of hospital stay, elevated infection risk, loss of lean muscle mass, increased mortality, delayed wound healing and prolonged ventilator time.1,6 If adequate nutrition support is not initiated in a person with a major burn, the subsequent malnutrition can reach a lethal level in just three to four weeks.2

If patients with burn injuries are unable to meet their nutrition requirements via oral diet, then enteric tube feeding is recommended. Enteral nutrition is defined as the provision of nutrients through the gastrointestinal tract.7 For the purposes of this research, "enteral feeding" will be used to define the provision of nutrients via an enteric feeding tube.

Guidelines vary as to the total body surface area (TBSA) percentage for which patients with burns should commence enteral feeding. For example, the Australian and New Zealand Burn Association recommends that children with greater than 15% TBSA involvement and adults with greater than 20% TBSA involvement should be assessed for enteral nutrition support.3 Similarly, the European Society for Clinical Nutrition and Metabolism-endorsed guidelines recommend that patients with major burns (greater than 20% TBSA) receive early nutritional therapy, preferentially by the enteral route.4 The International Society for Burn Injuries (ISBI) recommends that patients with greater than 20% TSBA involvement receive adequate calories and protein to meet their nutritional needs and that requirements should be calculated using a standardized equation; however, these recommendations acknowledge that in resource-limited countries, access to enteric feeding tubes and formulae may be limited. As a result, the ISBI clinical practice guidelines do not provide specific recommendations on the TBSA percentage for patients to commence enteric tube feeding but recommend optimizing nutrition using the best available resources.2 The most recent evidence-based, physician-authored clinical guidelines recommend that patients with moderate-to-severe burn injuries (> 20% TBSA) should receive enteral nutrition support. These recommendations also identify that burn patients with < 20% TBSA in at-risk groups, such as children, older adults and those with metabolic syndrome, may benefit from enteral nutrition support.8 Overall, enteral feeding is widely identified in literature as being a recommended and beneficial intervention in patients with > 20% TBSA burns and also in vulnerable patient sub-groups.

Nutrition delivered into the gastrointestinal tract is the preferred method of nutrition support for patients with burn injuries when compared to parenteral feeding.4 Parenteral nutrition is defined as the administration of nutrients by a route other than the alimentary canal.7 The recommendation to use enteral nutrition over parenteral nutrition is consistent across multiple nutritional care practice guidelines for burns with burn injuries.2-4,8,9

Oral and enteral fasting for theater has been identified as the most common cause of inadequate nutrition in patients with burn injuries.10,11 Despite this, numerous factors have been identified that cause these patients to miss out on nutrition. Other barriers to nutrition support may include elevated gastric residual volumes, dressing changes, prolonged therapy times, diagnostic tests performed away from the unit, dislodged feeding tubes, clogged feeding tubes, fasting for extubation, emesis and ileus.12 Although some causes of discontinuing enteral feeding may be unavoidable, long periods of imposed perioperative fasting may be unnecessary and may have a negative impact not only on overall energy intake but also on patient well-being, which can result in detrimental metabolic effects in patients with burn injuries.

The impact of perioperative fasting on energy deficits

The degree of energy deficits associated with perioperative fasting in patients with burn injuries has been investigated in a number of audits. For example, Winckworth et al. identified that adult and pediatric patients with burn injuries (mean 20% TBSA) experienced an average overall energy deficit of 12% per week due to perioperative fasting.13 Similarly, Lyons and Clemens retrospectively reviewed the nasogastric enteral nutrition of intubated and ventilated adult patients with burn injuries (> 20% TBSA and mean 40% TBSA). They found that the patients experienced a deficit of 18% of estimated energy requirements due to feeds being discontinued perioperatively.10 The nutritional deficits associated with perioperative fasting have the potential to impact patient recovery and outcomes such as mortality and wound infection, but further investigations are required.13

The impact of perioperative fasting on patient well-being

Fasting for surgery may not only cause nutritional deficits in patients with burn injuries but also could have deleterious effects on patients' well-being.14 Burn-specific studies identifying the impact of fasting on patient well-being have not been identified; however, a study by Tosun et al.15 evaluated the effects of preoperative fasting and fluid limitation in 99 patients undergoing laparoscopic cholecystectomy. They found that pre- and post-operative hunger, thirst, nausea and pain scores of patients fasting for longer than 12 hours were higher than those of patients fasting for less than 12 hours. Similarly, a systematic review by Bilku et al.16 assessed the role of preoperative carbohydrate loading on elective surgery patients. They concluded that pre-operative carbohydrate drinks significantly improved patient comfort after surgery, including reduced hunger, thirst, malaise, anxiety and nausea. An audit on perioperative fasting time in burn patients by Fu et al.17 revealed the average time from the last oral intake to resumption post-operatively was 15 hours and 20 minutes for solid food/enteral feeding. Although there is a lack of specific research on the impact of fasting on well-being in patients with burn injuries, there is evidence that these patients fast for extended periods of time, and, therefore, there is potential they will experience a similar negative impact on well-being with extended fasting times as other elective surgery patients.

The negative metabolic effects of perioperative fasting

Perioperative fasting may have negative metabolic effects. Although this topic has been widely discussed and researched in the general surgery patient population, there is a lack of burn-specific research and literature in this area. Insulin resistance develops as a response to virtually all types of surgical stress18 and is proportionate to the magnitude of surgery.19 Evidence suggests that insulin resistance is not beneficial on outcomes.18 Insulin resistance and hyperglycemia contribute to poor wound healing as well as muscle catabolism in patients with burn injuries.20 Avoiding preoperative fasting has been shown to be related to a substantial reduction in postoperative stress and insulin resistance in elective surgery patients.21 Two systematic reviews on elective surgery patients concluded that pre-operative carbohydrate intake may attenuate post-operative insulin resistance.16,22 Reduced fasting in patients with burn injuries may have positive metabolic effects; however, research in a burn-specific population is still needed to draw definitive conclusions.

Pre-operative fasting has historically been implemented to protect patients from potential adverse events. It aims to minimize the risk of regurgitation and pulmonary aspiration during non-emergency surgery involving anesthesia.23 Acute intraoperative aspiration is rare but is associated with substantial increased morbidity and hospital costs24,25; therefore, it is an important consideration in the care and safety of patients with burn injuries. The Australian and New Zealand College of Anaesthetists' current guidelines for children older than six months and adults are limited solid food (or breast milk/formula in infants) up to six hours prior to anesthesia and consumption of clear fluids at a maximum of 200 mL per hour up to two hours before surgery.14 The American Society of Anesthesiologists have similar practice guidelines and recommend a light meal up to six hours prior to procedures requiring anesthesia and non-alcoholic clear fluids up to two hours before surgery.23 Effective perioperative nutritional care of patients with burn injuries requires a balanced approach. The risk of aspiration needs to be minimized, as do nutritional deficits and the potential deleterious well-being and metabolic effects associated with fasting in the perioperative period.

There have been multiple possible strategies to increase the nutritional intake of patients with burn injuries during the perioperative period. Protocols aimed at reducing feeding stop times have demonstrated improved nutritional intakes in this patient population,26-28 but there is a lack of data on outcomes such as wound infection, length of hospital stay and mortality. Parenteral nutrition during surgery may enhance nutrient intake, although the literature suggests that the risk of parenteral nutrition may outweigh any potential benefits. Parenteral nutrition may increase the secretion of proinflammatory mediators and has been associated with liver dysfunction. It also increases the risk of infectious complication rates from catheter use. Additionally, parenteral nutrition supplementation in patients with burn injuries has been demonstrated to increase mortality compared to enteral nutrition.29 There is currently insufficient evidence supporting parenteral nutrition during surgery for patients with burn injures who have a functioning gastrointestinal tract.30

There is research specifically investigating the impact of perioperative nutrition on burn patient outcomes,28,31,32 with two similar methods reported. The first method is the continuation of enteral nutrition during theater via either post-pyloric feeding or intragastric feeding when patients have a previously protected airway (ventilated patients). The second method is enteral feeding up to two hours prior to surgery and immediately post-operatively (short fasting) in non-ventilated patients with nasogastric feeding tubes. It is, therefore, timely to investigate the results of these studies to determine whether increased perioperative feeding in patients with burn injuries can improve patient outcomes.

A preliminary search of the Cochrane Library, JBI Database of Systematic Reviews and Implementation Reports and PubMed located no systematic reviews completed or currently underway on this topic and no registered protocols with PROSPERO.

A search has been conducted for other similar systematic reviews on enteral feeding in burns patients. Two systematic reviews were identified; however, neither had comparable research topics. Wasiak et al.33 conducted a Cochrane systematic review on early versus delayed enteral nutrition support for patients with burn injuries. The authors identified three randomized controlled trials for inclusion in the review and concluded that the benefit of early enteral nutrition support on outcomes such as length of hospital stay and mortality remains inconclusive. A Cochrane review by Masters et al.34 investigated whether high-carbohydrate, high-protein, low-fat enteral feeding improved outcomes in burn patients compared to low-carbohydrate, high-protein, high-fat enteral feeds. The authors identified two studies for inclusion and concluded that the use of high-carbohydrate, low-fat enteral feeding might reduce the incidence of pneumonia compared with low-carbohydrate, high-fat feeding; however, there was inconclusive evidence on the effect on mortality. Although these two systematic reviews had some topic similarities, neither investigated perioperative enteral feeding in patients with burn injuries.

This systematic review will therefore aim to determine whether short fasting (nasogastric feeding up to two hours prior to theater and immediately thereafter) or nil fasting (nasogastric feeding in ventilated patients or post-pyloric feeding in non-ventilated patients) in patients with burn injuries will improve outcomes such as length of stay, wound infection and mortality. In addition, the review will investigate whether perioperative nutrition can be safely administered in patients with burn injuries without increasing the adverse event of perioperative aspiration pneumonia.

Review question

What is the effectiveness and safety of perioperative enteral nutrition in patients with burn injuries?

Inclusion criteria

Participants

This systematic review will consider studies that include either children (younger than 18 years) or adults (18 years or older) who have sustained an acute burn injury and undergo surgical management of their burn.

Studies that include patients with significant multi-trauma in addition to an acute burn injury will be excluded.

Interventions

This review will consider studies that evaluate patients who received perioperative enteral feeding. Perioperative enteral feeding will be defined as either:

a. Enteral feeding up to two hours prior to surgery and resumed within two hours post-surgery in patients receiving intragastric feeding; or

b. Continuous enteral feeding during surgery in patients with a previously secured airway (i.e. ventilated patients) and/or a post-pyloric feeding tube.

In this instance, enteral feeding will be defined as the delivery of a nutritional product that is delivered through an enteral feeding tube, regardless of the method of delivery (e.g. nasogastric, nasojejunal, naso-enteric, oro-gastric, percutaneous endoscopic gastrostomy or jejunal feeding tubes).

Those who received parenteral nutrition in addition to enteral nutrition during theater will be excluded.

Comparator

This review will consider studies that compare the interventions to patients who had enteral nutrition withheld for more than two hours prior to theater and experienced prolonged post-operative fasting (i.e. enteral feeding recommenced after return to the ward).

Outcomes

The following outcome measures will be included:

Primary outcomes

i. All-cause mortality

ii. Length of acute-care hospital stay

iii. Frequency of wound infection (as documented in medical records)

iv. Rate of wound healing (time to first donor site healing or time to wound closure)

v. Incidence of aspiration pneumonia (as documented in patient medical records)

Secondary outcomes

i. Energy deficit of patients who had enteral feeding withheld

ii. Patient-reported well-being and satisfaction, including hunger, thirst, nausea and vomiting

iii. Nitrogen balance

Where reported, other outcomes such as length of ventilator support time, skeletal muscle mass or time to mobilization, or any other relevant outcomes will be considered for inclusion.

Types of studies

This review will consider both experimental and quasi-experimental study designs (including randomized controlled trials, non-randomized controlled trials, before and after studies and interrupted time-series studies) and observational studies (including prospective and retrospective cohort studies, case-control studies and analytical cross-sectional studies). In the absence of sufficient experimental studies and observational studies, descriptive studies will be included in the review.

Methods

The proposed systematic review will be conducted in accordance with the JBI methodology for systematic reviews of effectiveness.35

Search strategy

The search strategy will aim to find both published and unpublished studies. The search strategy will be in three stages, in keeping with JBI methodology, to fully investigate the effectiveness of perioperative feeding in patients with burn injuries. An initial limited search of PubMed and CINAHL will be undertaken, followed by an analysis of the text words contained in the title and abstract, and of the index terms used to describe article. This will inform the development of a search strategy. A second comprehensive search using all identified keywords and index terms will then be undertaken across predefined databases. Thirdly, the reference list of all identified reports and articles will be searched for additional studies. Only studies published in English will be considered for inclusion in this review. There will be no date limits for the search.

Information sources

The information sources will include electronic databases and contact with study authors. The databases to be searched will include PubMed, CINAHL (EBSCOhost platform), Embase (Ovid platform), Web of Science, Cochrane Central Register of Controlled Trials and Scopus. Sources of unpublished studies and gray literature to be searched include ClinicalTrials.gov, Australian New Zealand Clinical Trials Register, European Clinical Trials Register, MedNar, SumSearch 2, ProQuest Dissertations and Theses, Google Scholar, OpenGrey, OpenDOAR, Openthesis.org, WHO International Clinical Trials Registry Platform, Latin American and Caribbean Health Sciences Literature (LILACS database) and AllTrials.

The details of the full search strategy for one database, PubMed, is provided in Appendix I.

Study selection

Following the search, all identified citations will be collated and uploaded into EndNote X8.1.0 (Clarivate Analytics, PA, USA) and duplicates removed. Titles and abstracts will then be screened by two independent reviewers for assessment against the inclusion criteria for the review. Studies that potentially meet the inclusion criteria will be retrieved in full and their details imported into the JBI System for the Unified Management, Assessment and Review of Information (JBI SUMARI; Joanna Briggs Institute, Adelaide, Australia). The full text of selected studies will be retrieved and assessed in detail against the inclusion criteria. Full-text studies that do not meet the inclusion criteria will be excluded, and reasons for exclusion will be provided in an appendix in the final systematic review report. Included studies will undergo a process of critical appraisal. The results of the search will be reported in full in the final report and presented in a Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) flow diagram.36 Any disagreements that arise between the reviewers will be resolved through discussion or with a third reviewer.

Assessment of methodological quality

Selected studies will be critically appraised by two independent reviewers for methodological quality using the standardized critical appraisal instruments from the JBI.35 Any disagreements that arise will be resolved through discussion or with a third reviewer. Following critical appraisal, studies that do not meet a certain quality threshold, based on relevant discussions and agreements with co-reviewers, will be excluded. The decision to exclude will be based on a predetermined list of decision rules to limit risk of bias. If the studies are of low methodological quality and fewer than five studies are identified for review, then all studies will be included, and a narrative describing the limitations in quality of the studies will be provided.

Data extraction

Data will be extracted from papers included in the review using the standardized data extraction tool available in JBI SUMARI35 by two independent reviewers. The data extracted will include specific details about the populations, interventions, study methods and outcomes of significance to the review question and specific objectives. In addition, attempts will be made to obtain missing data from the study report(s) by contacting the authors of the included papers. Any disagreements that arise between the reviewers will be resolved through discussion, or with a third reviewer. Data extraction will be carried out by one reviewer with verification by another reviewer to minimize bias and potential errors in data extraction.

Data synthesis

Papers will, where possible be pooled in a statistical meta-analysis using JBI SUMARI. Effect sizes will be expressed as either odds ratios (for dichotomous data) or weighted (or standardized) mean differences (for continuous data), and their 95% confidence intervals will be calculated for analysis. Heterogeneity will be assessed statistically using the standard chi-squared and I² tests. The choice of model (random or fixed effects) and method for meta-analysis will be based on the guidance by Tufanaru et al.37 Subgroup analyses (e.g. effects for children younger than 18 years compared to adults 18 years or older, severity of injury) will be conducted where there are sufficient data to investigate. Sensitivity analyses will be conducted to test decisions made regarding conducting meta-analysis with and without the inclusion of poor-quality studies. Where statistical pooling is not possible, the findings will be presented in narrative form including tables and figures to aid in data presentation where appropriate. A funnel plot will be generated to assess publication bias if there are 10 or more studies included in a meta-analysis. Statistical tests for funnel plot asymmetry (Egger test, Begg test, Harbord test) will be performed where appropriate.

Assessing certainty in the findings

A Summary of Findings will be created using GRADEpro software (McMaster University, ON, Canada). The GRADE approach for grading the quality of evidence will be followed. The Summary of Findings will present the following information where appropriate: absolute risks for treatment and control, estimates of relative risk and a ranking of the quality of the evidence based on study limitations (risk of bias), indirectness, inconsistency, imprecision and publication bias. This is provided in the Handbook published by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group.38

Acknowledgments

This review contributes toward a Masters of Clinical Science award for MC.

The authors acknowledge the contributions of Dr Sandeep Moola and Rochelle Kurmis for their feedback.

Appendix I: Search strategy for PubMed

Search conducted on 26 September 2018

References