Early versus delayed enteral nutrition support in patients with thermal injuries
Abstract
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:
The objective of this review is to establish the relative effectiveness of early versus delayed enteral nutrition support in patients with thermal injuries.
Background
The type of formula and timing of enteral nutrition support in patients with thermal injuries has long been debated. What is known is that burn injury can result in profound metabolic abnormalities, increased infection risks, decreased healing rates, and altered cell function. The rapid removal of devitalized burn tissue, combined with early nutritional support, appears to significantly attenuate this auto‐destructive process (Demling 2000).
After the thermal injury has occurred a cascade of events are set into motion from the outset. The initial "Ebb" phase occurs immediately after the thermal injury and manifests as hypovolemia and tissue hypoxia due to poor cardiac output and increased oxygen consumption, ultimately leading to shock. The "Flow" phase occurs 12 to 24 hours post the initial insult as the patient becomes fluid resuscitated and when a return of an adequate oxygen transport occurs. At this stage an increase in glucose production and free fatty acid release will take place (Mahan 1996). The metabolic response to burns is complex and is illustrated by an accelerated catabolism leading to a negative nitrogen balance and loss of lean body tissue (primarily skeletal muscle).
Patients with larger burns have significant energy requirements. These patients as well as those with inhalation injuries and/or who require mechanical ventilation from several days to weeks may not be able to meet their requirements for macro‐ and micronutrients (i.e. food and fluids) via the oral route. This is when enteral nutrition support becomes one of the primary interventions.
Enteral nutrition is provided by placing a flexible feeding tube via the nose, mouth or a formed tract through the abdominal wall, into the gastric or small bowel region. The feeding tube delivers liquid nutritional formula (enteral nutrition), which contains macro‐ and micronutrients. Enteral nutrition will be provided until sufficient oral intake is established to meet the patient's requirements.
The Eastern Association for the Surgery of Trauma (EAST) group (EAST 2001) recommends that enteral nutrition should ideally begin during resuscitation in a patient with severe burns, but a fear of complications normally delays enteral support until after the resuscitation period has transpired (McDonald 1991).
Many studies have investigated the outcomes when patients have received early versus delayed enteral feeding. Thomas 2001 concisely discusses the restriction of enteral nutrition support normally taking place due to a perceived risk of ileus, as a result of a reduced blood flow to the gastrointestinal region. But, she suggests that actually feeding within several hours of the burn injury can prevent this from taking place. Thomas 2001 also reports that the hypermetabolic response may be blunted and gut integrity maintained when enteral nutrition support is provided early, thus reducing the risk of gut‐origin sepsis secondary to bacterial translocation.
Several other authors support the findings that early enteral feeding can maintain the gastrointestinal mass and function (Gottschlich 2002), minimise bacterial translocation (Gottschlich 2002; Peng 2001; Zhu 2003), reduce gastroparesis (EAST 2001; Hansbrough 1993) and prevent hypermetabolism (Hart 2003; Mochizuki 2003; Wang 1997). While others studies have shown no advantage and possible disadvantages of early enteral feeding. Peck et al (Peck 2004) showed that providing early enteral support did not moderate hypermetabolism, and Gottschlich 2002 reports that hypotension, shock, splanchnic hypoperfusion, and intestinal necrosis might all be associated with early enteral nutrition support.
There is also a debate over what is considered the time frame of early enteral nutrition support. Gottschlich 2002 reports on studies beginning enteral nutrition from as early as two hours and as late as five days post injury. Most studies consider 'early' as 24 to 48 hours post the initial thermal injury. For the purpose of this review early enteral nutrition will be considered to be less than 24 hours.
Given the variety opinions and interventions currently being researched and implemented it is hoped that clear evidence can be established as to whether early versus delayed enteral nutrition support is safe, effective and beneficial to patient outcomes (i.e. infection rates, wound healing, mortality and length of stay), with thermal injuries.
Objectives
The objective of this review is to establish the relative effectiveness of early versus delayed enteral nutrition support in patients with thermal injuries.
Methods
Criteria for considering studies for this review
Types of studies
All randomised controlled trials (RCTs) that evaluate the safety and effectiveness of early versus delayed feeding in burns patients. No quasi RCTs will be examined.
Types of participants
All adults (>16years) with any thermal injury to the epidermis, subcutaneous tissues, vessels, nerve, tendons, or bone will be included.
Types of interventions
Early enteral feeding (within 24 hours of injury) versus delayed enteral feeding (greater than 25 hours).
Where enteral nutrition (EN) is the delivery of a liquid nutritional formula, which contains macro‐ and micronutrients that passes any part of the digestive tract, regardless of the method of deliver (e.g. Nasogastric, naso‐jejunal, naso‐enteric, oro‐gastric, PEG or jejunal feeding tubes).
Types of outcome measures
Clinically important measures of effectiveness will be selected and are as follows:
Primary outcomes;
1. All cause mortality at end of follow‐up
2. Length of hospital stay
3. Frequency of infection
4. Number of adverse events such as bowel necrosis, acute respiratory distress syndrome, renal failure, multisystem organ failure.
Secondary outcomes;
1. Weight
2. Biochemical markers such as albumin, white cell count and C‐reactive protein.
Secondary parameters such as those listed above will be considered if reported in the studies.
Search methods for identification of studies
It is our intention to capture both published and unpublished trials. Relevant trials will be identified in the Cochrane Central Register of Controlled Trials (CENTRAL, latest issue), MEDLINE (1966 to present), EMBASE (1980 to present), CINAHL (1982 to present), and any additional relevant medical databases. No language restrictions will be applied.
The following search strategy will be used for MEDLINE and adapted for the other databases:
1. explode Burns/
2. burn*.ab, ti
3. thermal next injur*.ab, ti
4. or/1‐3
5. explode Enteral‐Nutrition/
6. explode Feeding‐Methods/
7. ( ((alimentary canal or gastrointestinal or enteral or oral* or sip or gastric or tube* or method*) near feed*) in AB )or( ((alimentary canal or gastrointestinal or enteral or oral* or sip or gastric or tube* or method*)near feed*) in TI )
8. ( (enteral next (feed* or nutrition*)) in TI )or( (enteral next (feed* or nutrition*)) in AB )
9. ( ((nasogastric or gastrostomy or jejunostomy or gastric) near tube*) in TI )or( ((nasogastric or gastrostomy or jejunostomy or gastric) near tube*) in AB )
10. or/5‐9
11. 4 and 10
12.( (early or delay*) in TI )or( (early or delay*) in AB )
13. 11 and 12
In addition, we will contact experts in the field of burns and nutrition; contact authors of relevant studies to request details of unpublished or ongoing investigations and hand search relevant journals with the assistance of our review group.
Data collection and analysis
Trial identification
Records retrieved by the initial search will be scanned by JW and RJ to exclude obviously irrelevant studies. Two authors (RJ and HC) will then identify trials that may meet the inclusion criteria. Full‐text articles will be retrieved and reviewed by three authors (JW, RJ, and HC) for the purpose of applying inclusion criteria independently. In all instances, differences of opinion will be resolved by discussion.
Data extraction
Data from the studies will be extracted independently by three authors (JW, RJ, and HC) using standardised forms developed for this review. Data extracted will include: study characteristics, study design, participant demographics, inclusion/exclusion criteria lists, intervention and comparison details plus outcomes measures and results. All differences will be resolved by discussion. The original study investigators will be contacted to provide information if missing data are encountered or if necessary data, such as adverse events, are not clearly stated.
Quality assessment
Study quality will be assessed using an adaptation of the method outlined in Schulz 1995. Results from the study quality assessment will be presented in a descriptive manner. The following characteristics will be assessed:
Adequacy of the randomisation process;
A: Adequate sequence generation is reported using random number tables, computer random number generator, coin tossing, or shuffling
B: Did not specify one of the adequate reported methods in (A) but mentioned randomisation method
C: Other methods of allocation that appear to be unbiased.
Adequacy of the allocation concealment process;
A: Adequate measures to conceal allocation such as central randomisation; serially numbered, opaque, sealed envelopes; or other description that contained convincing elements of concealment
B: Unclearly concealed trials in which the author either did not report an allocation concealment approach at all, or reported an approach that did not fall into one of the categories in (A)
C: Inadequately concealed trials in which method of allocation is not concealed, such as alteration methods or use of case record numbers
Potential for selection bias after allocation;
A: Trials where an intention‐to‐treat analysis is possible and few losses to follow up are noted.
B: Trials that reported exclusions (as listed in (A) but exclusions were less than 10%).
C: No reporting on exclusions, or exclusions greater than 10%, or wide differences in exclusions between groups.
Level of masking (treatment provider, patient, outcome assessor);
A: Double‐ or triple‐blind
B: Single‐blind
C: Non‐blind.
Analyses
We propose to use a fixed‐effect model where there is no evidence of significant heterogeneity between studies, and employ a random effects model when such heterogeneity is likely (DerSimonian 1986). Consideration will be given to the appropriateness of meta‐analysis in the presence of significant clinical or statistical heterogeneity. Statistical heterogeneity will be assessed using the I2 statistic. Heterogeneity will be explored and subgroup analyses will be performed if appropriate.
For proportions (dichotomous outcomes), Relative risk (RR) will be used. Continuous data will be converted to the weighted mean difference (WMD) using the inverse variance method and an overall WMD will be calculated. Publication bias will be investigated using funnel plots or other corrective analytical methods, depending on the number of clinical trials included in the systematic review.
Where appropriate data exist, we will consider subgroup analyses based on method of feeing i.e. jejunal versus gastric, nasogastric versus naso‐jejunal. Subgroup analysis will be performed where appropriate by calculation of RR or WMD in each subgroup and examination of the 95% confidence intervals. Non‐overlap in intervals will be taken to indicate a statistically significant difference between subgroups.
All analyses will be made on an intention‐to‐treat basis where possible, and where not possible this will be clearly stated.
