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/m. 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. The prevalence of obese patients in intensive care largely mirrors that of the general population. 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. 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. 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. 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. 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. 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. 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. There is also altered mobilization of fuel stores, futile cycling, and evidence of altered lipoprotein metabolism. 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. 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. 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. 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.The provision of adequate nutrition has become an integral component of supportive ICU care, but is complex. 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. 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.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. 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.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. 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. 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. 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. In fact obesity does not necessarily protect from malnutrition, particularly protein and micronutrient malnutrition. 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. This would be consistent with the large body of evidence that associates malnutrition (BMI < 20 kg/m) with increased mortality, and has led some authors to postulate that the weight-mortality relationship is U-shaped. 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.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. 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. 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. 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.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.