Feeding the critically ill obese patient: a systematic review protocol : JBI Evidence Synthesis

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SYSTEMATIC REVIEW PROTOCOLS

Feeding the critically ill obese patient: a systematic review protocol

Secombe, Paul; Harley, Simon; Chapman, Marianne; Aromataris, Edoardo

Author Information

1The Joanna Briggs Institute, Faculty of Health Science, University of Adelaide, Australia

2School of Medicine, University of Adelaide, Australia

3Alice Springs Hospital, Alice Springs, Australia

4Royal Adelaide Hospital, Adelaide, Australia

Corresponding author:

Paul Secombe

[email protected]

JBI Database of Systematic Reviews and Implementation Reports 13(10):p 95-109, October 2015. | DOI: 10.11124/jbisrir-2015-2458
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Abstract

Review question/objective 

The objective of this review is to identify effective enteral nutritional regimens targeting protein and calorie delivery for the critically ill obese patient on morbidity and mortality.

More specifically, the review question is:

In the critically ill obese patient, what is the optimal enteral protein and calorie target that improves mortality and morbidity?

Background 

The World Health Organization (WHO) defines obesity as abnormal or excessive fat accumulation that may impair health, or, empirically, as a body mass index (BMI) ≥ 30 kg/m2.1,2 Twenty-eight percent of the Australian population is obese with the prevalence rising to 44% in rural areas, and there is evidence that rates of obesity are increasing.3-5 The prevalence of obese patients in intensive care largely mirrors that of the general population.6,7 There is concern, however, that this may also be rising. A recently published multi-center nutritional study of critically ill patients reported a mean BMI of 29 in their sample, suggesting that just under 50% of their intensive care population is obese.8 It is inevitable, therefore, that the intensivist will care for the critically ill obese patient.

Managing the critically ill obese patient is challenging, not least due to the co-morbid diseases frequently associated with obesity, including diabetes mellitus, cardiovascular disease, dyslipidaemia, sleep disordered breathing and respiratory insufficiency, hepatic steatohepatitis, chronic kidney disease and hypertension.7,9-14 There is also evidence that metabolic processes differ in the obese patient, particularly those with underlying insulin resistance, itself a marker of the metabolic syndrome, which may predispose to futile cycling, altered fuel utilization and protein catabolism.14-21 These issues are compounded by altered drug pharmacokinetics, and the additional logistical issues associated with prophylactic, therapeutic and diagnostic interventions.

It is entirely plausible that the altered metabolic processes observed in the obese intensify and compound the metabolic changes that occur during critical illness. The early phases of critical illness are characterized by an increase in energy expenditure, resulting in a catabolic state driven by the stress response.22-24 Activation of the stress response involves up-regulation of the sympathetic nervous system and the release of pituitary hormones resulting in altered cortisol metabolism and elevated levels of endogenous catecholamines.25-27 These produce a range of metabolic disturbances including stress hyperglycemia, arising from both peripheral resistance to the effects of anabolic factors (predominantly insulin) and increased hepatic gluconeogenesis.26,27 Proteolysis is accelerated, releasing amino acids that are thought to be important in supporting tissue repair, immune defense and the synthesis of acute phase reactants.28,29 There is also altered mobilization of fuel stores, futile cycling, and evidence of altered lipoprotein metabolism.15,20,26,30 In the short term this is likely to be an adaptive response, but with time and ongoing inflammation this becomes maladaptive with a concomitant risk of protein-calorie malnutrition, immunosuppression and wasting of functional muscle tissue resulting from protein catabolism, and this is further compounded by disuse atrophy.20,27,31-33 Muscle atrophy and intensive care unit (ICU) acquired weakness is complex and poorly understood, but it is postulated that the provision of calories and sufficient protein to avoid a negative nitrogen balance mitigates this process.28 Avoiding lean muscle mass loss in the obese intuitively has substantial implications, given the larger mass that is required to be mobilized during their rehabilitation phase.

There is, in addition, evolving evidence that hormones derived from both the gut and adipose tissue are also involved in the response to stress and critical illness, and that adipose tissue in particular is not a benign tissue bed, but rather should be considered an endocrine organ.18,34-36 Some of these hormones are thought to be pro-inflammatory and some anti-inflammatory; however both the net result and clinical significance of these are yet to be fully elucidated.18,27,34

The provision of adequate nutrition has become an integral component of supportive ICU care, but is complex.13 There is ongoing debate within critical care literature regarding the optimal route of delivery, the target dose, and the macronutrient components (proportion of protein and non-protein calories) of nutritional support.13,27 A number of studies have associated caloric deficit with morbidity and mortality, with the resultant assumption that prescribing sufficient calories to match energy expenditure will reduce morbidity and mortality, although the evidence base underpinning this assumption is limited to observational studies and small, randomized trials.13,32,37-43

There is research available that suggests hyper-caloric feeding or hyper-alimentation, particularly of carbohydrates, may result in increased morbidity including hyperglycemia, liver steatosis, respiratory insufficiency with prolonged duration of mechanical ventilation, re-feeding syndrome and immune suppression.27,44-49 But the results from studies of hypo-caloric and eucaloric feeding regimens in critically ill patients are conflicting, independent of the added metabolic complexities observed in the critically ill obese patient.8,13,40,49

Notwithstanding the debate regarding the dose and components of nutritional therapy, there is consensus that nutrition should be provided, preferably via the enteral route, and preferably initiated early in the ICU admission.50-52 The enteral route is preferred for a variety of reasons, not the least of which is cost. In addition there is evidence to suggest the enteral route is associated with the maintenance of gut integrity, a reduction in bacterial translocation and infection rates, a reduction in the incidence of stress ulceration, attenuation of oxidative stress, release of incretins and other entero-hormones, and modulation of systemic immune responses.20,27,52-57 Yet there is evidence that the initiation of enteral nutritional support for the obese critically ill patient is delayed, and that when delivered is at sub-optimal levels.32,58 The reasons for this remain obscure, but may be associated with the false assumption that every obese patient has nutritional reserves due to their adipose tissues, and can therefore withstand longer periods with no, or reduced nutritional support.58 In fact obesity does not necessarily protect from malnutrition, particularly protein and micronutrient malnutrition.7,20,59-63 It has been suggested by some authors that the malnutrition status of critically ill patients is a stronger predictor of mortality than BMI, and that once malnutrition status is controlled for, the apparent protective effects of obesity observed in several epidemiological studies dissipate.7,64-73 This would be consistent with the large body of evidence that associates malnutrition (BMI < 20 kg/m2) with increased mortality, and has led some authors to postulate that the weight-mortality relationship is U-shaped.13,74-82 This has proven difficult to demonstrate, however, due to recognized confounding influences such as chronic co-morbidities, baseline nutritional status and the nature of the presenting critical illness.13

This has led to interest in nutritional regimens targeting alternative calorie and protein goals to protect the obese critically ill patient from complications arising from critical illness, and particularly protein catabolism. However, of the three major nutritional organizations, the American Society of Parenteral and Enteral Nutrition (ASPEN) is the only professional organization to make specific recommendations about providing enteral nutritional support to the critically ill obese patient, recommending a regimen targeting a hypo-caloric, high-protein goal.20 It is thought that this regimen, in which 60-70% of caloric requirements are provided promotes steady weight loss, while providing sufficient protein to achieve a neutral, or slightly positive, nitrogen balance, mitigating lean muscle mass loss, and allowing for wound healing.54 Targeting weight loss is proposed to improve insulin sensitivity, improve nursing care and reduce the risk of co-morbidities, although how this occurs and whether it can occur over the relatively short time frame of an intensive care admission (days to weeks) remains unclear.54 Despite these recommendations observational data of international nutritional practice suggest that ICU patients are fed uniformly low levels of calories and protein across BMI groups.32

Supporting the critically ill obese patient will become an increasingly important skill in the intensivist's armamentarium, and enteral nutritional therapy forms a cornerstone of this support. Yet, neither the optimal total caloric goal nor the macronutrient components of a feeding regimen for the critically ill obese patient is evident. Although the suggestion that altering the macronutrient goals for this vulnerable group of patients appears to have a sound physiological basis, the level of evidence supporting this remains unclear, and there are no systematic reviews on this topic. The aim of this systematic review is to evaluate existing literature to determine the best available evidence describing a nutritional strategy that targets energy and protein delivery to reduce morbidity and mortality for the obese patient who is critically ill.

Inclusion criteria

Types of participants

This review will consider studies that include critically ill obese adult patients receiving enteral nutritional support at any stage during their ICU admission for a time period of greater than 72 hours. Studies eligible for retrieval will include intensive care patients in intensive care units or alternatively using a population of patients in which greater than or equal to 50% of trial participants required mechanical ventilation. In attempting to limit the search to studies involving critically ill patients in this way, it is acknowledged that there are differing criteria that determine ICU admission between countries determined in part by resources, in part by cultural differences and in part by the model of intensive care that predominates (closed versus open intensive care units). This is, however, a universal conundrum of critical care research in which there is often heterogeneity in admission diagnosis, severity of disease, metabolic derangement and therapeutic interventions, and which has been recognized in other publications.83

Critically ill populations comprising both elective and emergency ICU admissions will be included, as will critically ill populations with a medical or surgical admission diagnosis.

The WHO definition of obesity will be used in this review, i.e. a BMI ≥ 30 kg/m2, where BMI is body mass in kilograms divided by the square of body height in meters.1,2

Studies examining a pediatric population, or using parenteral routes of administration will be excluded.

Types of intervention(s)/phenomena of interest

This review will consider all studies that compare any enteral feeding/nutritional regimen that specify a goal protein and calorie target. Nutritional therapy regimens can be defined by both their targeted caloric goal and the amount of targeted protein. With regard to total targeted calories these are likely to fall into categories that will be defined as hypo-caloric (< 20 kcal/kg/day), eu-caloric (20-30 kcal/kg/day), and hyper-caloric (> 30 kcal/kg/day). Targeted protein delivery can be categorized as low protein (< 1 g/kg/day), moderate protein (1-2 g/kg/day) and high protein (> 2 g/kg/day).

Types of outcomes

Outcomes of interest in this review are chosen primarily for their importance in patient centered outcomes, while most of the secondary outcomes are chosen as surrogate markers of morbidity.

The primary outcome for this review will be mortality.

Secondary outcomes sought will include mortality at pre-defined endpoints (ICU discharge, 30 days, 60 days and 90 days). Other secondary outcomes will include ICU and hospital length of stay or their corollary ICU and hospital free days, duration of mechanical ventilation or its corollary ventilator free days, nitrogen balance, azotemia (blood urea nitrogen), acute kidney injury, the incidence of nosocomial infection, weight loss or change in BMI, gastro-intestinal intolerance (high gastric residual volume, vomiting or diarrhea) and insulin requirement.

Nitrogen balance has been chosen as a surrogate marker of the adequacy of protein supplementation and is calculated using formulae allowing for protein intake and 24 hour urinary protein excretion.84 Azotemia (serum urea) and renal injury using the Acute Dialysis Quality Initiative (ADQI) definition (RIFLE - Risk, Injury, Failure, Loss of function, End stage renal disease) have been chosen as markers of potential harm related to the inability to clear protein metabolites.85 The incidence of nosocomial infection is important since an association between nutritional status and nosocomial infection incidence has been identified in a number of studies.37,74,86 Since weight loss is one proposed benefit from the ASPEN recommended prescription of a hypo-caloric high-protein regimen, change in weight or a change in BMI will also be sought, while gastro-intestinal intolerance is a common adverse event with nutritional regimens and will also be a secondary outcome.20 Finally, given the experimental findings that indicate high glucose concentrations have a range of negative effects, including increasing the production or expression (or both) of pro-inflammatory mediators, decreased chemotaxis and phagocytosis, alteration in leukocyte adherence, reduced release of reactive oxygen species from neutrophils and alterations in endothelial integrity, insulin requirement has been chosen as a surrogate marker of glycemic control. In addition, given the range of metabolic disturbances seen in the critically ill obese patient, glycemic control is arguably more important in this group than in their lean counterparts.19,20,27

Types of studies

Studies eligible for retrieval will include, in the first instance, randomized controlled studies. In the absence of randomized controlled trials, any study with a non-randomized control, quasi-experimental, controlled before and after, or cohort study (whether prospective or retrospective) design will be considered for inclusion in order to provide a sufficient evidence base to inform on the effectiveness of different feeding regimes targeting calories and protein in the critically ill obese patient.

Search strategy

The search strategy will involve a three step process. An initial limited search of PubMed and CINAHL will be undertaken, followed by an analysis of keywords contained in the titles and abstracts, and of the index terms used to describe the article. A second search with all identified key words will be undertaken across PubMed, Embase, ProQuest Dissertations and Theses and conference papers index, CINAHL, Cochrane Central Trials Register, and the WHO Clinical Trials Register. Only studies published in English will be eligible for retrieval, and there will be no date limits applied. Thirdly the reference list of all identified reports and articles will be searched for additional studies.

Initial key words to be used will be; ("critically ill" OR "intensive care") AND (obese OR overweight) AND (nutrition OR diet OR feed*).

Assessment of methodological quality

Quantitative papers selected for retrieval will be assessed by two independent reviewers for methodological validity prior to inclusion in the review using standardized critical appraisal instruments from the Joanna Briggs Institute Meta Analysis of Statistics Assessment and Review Instrument (JBI-MAStARI) which is found in Appendix I. Any disagreement will be resolved through discussion, or with a third reviewer.

Data extraction

Quantitative data will be extracted from papers included in the review using the standardized data extraction tool from JBI-MAStARI (Appendix II). The data extracted will include specific details about the intervention(s), populations, study methods and outcomes of significance to the review question and specific objectives. Authors will be contacted for further information if required.

Data synthesis

Analysis will be conducted on all primary and secondary outcomes where possible. Quantitative data will, where possible, be pooled in a statistical meta-analysis using JBI-MAStARI. All results will be subject to double data entry. Effect sizes expressed as odds ratio (for categorical data) and weighted mean differences (for continuous data) and their 95% confidence intervals will be calculated for analysis. Decisions regarding the choice of meta-analytical models will be informed by the JBI reviewers manual.87 Where statistical pooling is not possible, the findings will be presented in narrative form.

If there is sufficient data, further exploratory synthesis and subgroup analysis performed on the basis of ICU admission type (medical versus surgical and emergent versus elective) will be carried out to explore anticipated heterogeneity across studies. These subgroups will be considered as there is evidence that admission type effects ICU mortality.88 Furthermore, since it is possible that older patients paradoxically require more protein to achieve a neutral nitrogen balance, while having a lower glomerular filtration rate, a comparison of outcomes in a cohort of younger patients (< 60 years of age), compared to older patients (> 60 years of age) would be appropriate.84

Conflicts of interest

There are no conflicts of interest to declare.

Acknowledgements

The authors would like to acknowledge A/Professor Adam Deane, Intensivist, Royal Adelaide Hospital, for contributing ideas and support, and Dr Penny Stewart, Director Intensive Care, Alice Springs Hospital, for support of this project.

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                                    Appendix I: Appraisal instruments

                                    MAStARI appraisal instrument

                                    FU1-11
                                    Figure:
                                    no caption available
                                    FU2-11
                                    Figure:
                                    no caption available

                                    Appendix II: Data extraction instruments

                                    MAStARI data extraction instrument

                                    FU3-11
                                    Figure:
                                    no caption available
                                    FU4-11
                                    Figure:
                                    no caption available
                                    Keywords:

                                    body composition; critical illness; critical care; diet; enteral nutrition; feeding method; intensive care unit; nutritional therapy; obese

                                    © 2015 by Lippincott williams & Wilkins, Inc.