Martin D. Rosenthal

When Is It Appropriate to Use Arginine in Critical Illness

In health, arginine is considered a nonessential amino acid but can become an essential amino acid (ie, conditionally essential amino acid) during periods of metabolic or traumatic stress as endogenous arginine supply is inadequate to meet physiologic demands. Arginine depletion in critical illness is associated with impairments in microcirculatory blood flow, impaired wound healing, and T-cell dysfunction. The purpose of this review is to (1) describe arginine metabolism and role in health and critical illness, (2) describe the relationship between arginine and asymmetric dimethylarginine, and (3) review studies of supplemental arginine in critically ill patients.

The Critical Care Obesity Paradox and Implications for Nutrition Support

Obesity is a leading cause of preventable death worldwide. The prevalence of obesity has been increasing and is associated with an increased risk for other co-morbidities. In the critical care setting, nearly one third of patients are obese. Obese critically ill patients pose significant physical and on-physical challenges to providers, including optimization of nutrition therapy. Intuitively, obese patients would have worse critical care-related outcome. On the contrary, emerging data suggests that critically ill obese patients have improved outcomes, and this phenomenon has been coined “the obesity paradox.” The purposes of this review will be to outline the historical views and pathophysiology of obesity and epidemiology of obesity, describe the challenges associated with obesity in the intensive care unit setting, review critical care outcomes in the obese, define the obesity-critical care paradox, and identify the challenges and role of nutrition support in the critically ill obese patient.

The gut in trauma.

Purpose of reviewThe purpose of this review is to describe established and emerging mechanisms of gut injury and dysfunction in trauma, describe emerging strategies to improve gut dysfunction, detail the effect of trauma on the gut microbiome, and describe the gut–brain connection in traumatic brain injury. Recent findingsNewer data suggest intraluminal contents, pancreatic enzymes, and hepatobiliary factors disrupt the intestinal mucosal layer. These mechanisms serve to perpetuate the inflammatory response leading to multiple organ dysfunction syndrome (MODS). To date, therapies to mitigate acute gut dysfunction have included enteral nutrition and immunonutrition; emerging therapies aimed to intestinal mucosal layer disruption, however, include protease inhibitors such as tranexamic acid, parenteral nutrition-supplemented bombesin, and hypothermia. Clinical trials to demonstrate benefit in humans are needed before widespread applications can be recommended. SummaryDespite resuscitation, gut dysfunction promotes distant organ injury. In addition, postresuscitation nosocomial and iatrogenic ‘hits’ exaggerate the immune response, contributing to MODS. This was a provocative concept, suggesting infectious and noninfectious causes of inflammation may trigger, heighten, and perpetuate an inflammatory response culminating in MODS and death. Emerging evidence suggests posttraumatic injury mechanisms, such as intestinal mucosal disruption and shifting of the gut microbiome to a pathobiome. In addition, traumatic brain injury activates the gut–brain axis and increases intestinal permeability.

PATTERNS OF GENE EXPRESSION AMONG MURINE MODELS OF HEMORRHAGIC SHOCK/TRAUMA AND SEPSIS

Controversy remains whether the leukocyte genomic response to trauma or sepsis is dependent upon the initiating stimulus. Previous work illustrated poor correlations between historical models of murine trauma and sepsis (i.e., trauma-hemorrhage and lipopolysaccharide injection, respectively). The aim of this study is to examine the early genomic response in improved murine models of sepsis [cecal ligation and puncture (CLP)] and trauma [polytrauma (PT)] with and without pneumonia (PT+Pp). Groups of naïve, CLP, PT, and PT+Pp mice were killed at 2 h, 1 or 3 days. Total leukocytes were isolated for genome-wide expression analysis, and genes that were found to differ from control (false discovery rate adjusted P < 0.001) were assessed for fold-change differences. Spearman correlations were also performed. For all time points combined (CLP, PT, PT+Pp), there were 10,426 total genes that were found to significantly differ from naïve controls. At 2 h, the transcriptomic changes between CLP and PT showed a positive correlation (rs) of 0.446 (P < 0.0001) but were less positive thereafter. Correlations were significantly improved when we limited the analysis to common genes whose expression differed by a 1.5 fold-change. Both pathway and upstream analyses revealed the activation of genes known to be associated with pathogen-associated and damage-associated molecular pattern signaling, and early activation patterns of expression were very similar between polytrauma and sepsis at the earliest time points. This study demonstrates that the early leukocyte genomic response to sepsis and trauma are very similar in mice.

Persistent, Immunosuppression, Inflammation, Catabolism Syndrome and Diaphragmatic Dysfunction

Purpose of reviewThe purpose of this review is to explore the relationship between ICU-acquired weakness, diaphragm dysfunction, and persistent immunosuppression, inflammation, catabolism syndrome (PICS), as well as if there are any therapies that can help rehabilitate these patients.Recent findingsLiterature pertaining to PICS is scant, as it is a relatively new description of encompassing chronic multiorgan dysfunction and chronic critical illness. PICS patients invariably have persistent diaphragm dysfunction and ICU-acquired weakness. To better understand how severe each state is and how they are related, the literature was reviewed.SummaryCombating diaphragm dysfunction, ICU-acquired weakness, and PICS is a difficult task for intensivists. There are certain nutritional supplements that can help rehabilitate these patients, but there is no silver bullet right now. Helping these patients currently takes a multimodal approach.

Chronic Critical Illness: Application of What We Know

Over the last decade, chronic critical illness (CCI) has emerged as an epidemic in intensive care unit (ICU) survivors worldwide. Advances in ICU technology and implementation of evidence-based care bundles have significantly decreased early deaths and have allowed patients to survive previously lethal multiple organ failure (MOF). Many MOF survivors, however, experience a persistent dysregulated immune response that is causing an increasingly predominant clinical phenotype called the persistent inflammation, immunosuppression, and catabolism syndrome (PICS). The elderly are especially vulnerable; thus, as the population ages the prevalence of this CCI/PICS clinical trajectory will undoubtedly grow. Unfortunately, there are no proven therapies to prevent PICS, and multimodality interventions will be required. The purpose of this review is to: (1) discuss CCI as it relates to PICS, (2) identify the burden on healthcare and poor outcomes of these patients, and (3) describe possible nutrition interventions for the CCI/PICS phenotype.

Intermittent versus continuous feeding in critically ill adults

Purpose of review Early enteral nutrition is recommended in critically ill adult patients. The optimal method of administering enteral nutrition remains unknown. Continuous enteral nutrition administration in critically ill patients remains the most common practice worldwide; however, its practice has recently been called into question in favor of intermittent enteral nutrition administration, where volume is infused multiple times per day. This review will outline the key differences between continuous and intermittent enteral nutrition, describe the metabolic responses to continuous and intermittent enteral nutrition administration and outline recent studies comparing continuous with intermittent enteral nutrition administration on outcomes in critically ill adults. Recent findings In separate studies, healthy humans and critically ill patients receiving intermittent nutrition (infused over 3 h) had improved whole body protein balance from negative to positive. These studies did not have an isonitrogenous control group. A randomized controlled trial of intermittent bolus versus continuous enteral nutrition in healthy humans found that intermittent bolus feeding increased mesenteric arterial blood flow, increased insulin and peptide YY and reduced blood glucose concentration. A randomized controlled trial comparing intermittent bolus to continuous enteral nutrition in critically ill patients did not demonstrate clinically relevant differences in glycemic variability, insulin use or tube feeding volume or caloric intake between the two groups. Summary Studies in healthy humans suggest that intermittent nutrient administration, as opposed to continuous, improves whole body protein synthesis. Unfortunately, similarly designed studies are lacking for critically ill patients. Future studies evaluating the impact of intermittent versus continuous nutrition administration on critical care outcomes should take into account factors such as protein quantity, protein quality and delivery route (enteral and/or parenteral). Until further studies are conducted in critically ill patients, a recommendation for or against intermittent nutrition delivery cannot be made.

Nutritional Support for Abdominal Sepsis

Intra-abdominal sepsis can be a challenging pathophysiologic state. There are a lot of misconceptions surrounding nutrition supplementation in patients with intra-abdominal sepsis. Persistent inflammation immunosuppression catabolism syndrome (PICS) is a new phenotype of multiple organ failure associated with a severe stress such as intra-abdominal sepsis. Nutritional support of these patients is paramount to their recovery and should still largely follow the ASPEN guidelines. Certain nutritional adjuncts could ultimately prove to provide benefit in treating patients with intra-abdominal sepsis and PICS.

Can Specialized Pro-resolving Mediators Deliver Benefit Originally Expected from Fish Oil?

Purpose of the ReviewFish oil (FO) supplementation has historically been used by individuals suffering from cardiovascular disease and other inflammatory processes. However, a meta-analysis of several large randomized control trials (RCTs) suggested FO conferred no benefit in reducing cardiovascular risk. Skeptics surmised that the lack of benefit was related to FO dose or drug interactions; therefore, the widely accepted practice of FO consumption was brought into question.Recent FindingsThereafter, Serhan et al. identified specialized pro-resolving mediators (SPMs) to be one of the bioactive components and mechanisms of action of FO. SPMs are thought to enhance resolution of inflammation, as opposed to classic anti-inflammatory agents which inhibit inflammatory pathways. Numerous diseases, including persistent Inflammation, immunosuppression, and catabolic syndrome (PICS), are rooted in a burden of chronic inflammation. SPMs are gaining traction as potential therapeutic agents used to resolve inflammation in cardiovascular disorders, inflammatory bowel disease, sepsis, pancreatitis, and acute respiratory distress syndrome (ARDS).SummaryThis narrative reviews the history of FO and the various studies that made the health benefits of FO inconclusive, as well as an overview of SPMs and their use in specific disease states.

Tempering the Clinical Effects of Early Myeloid-derived Suppressor Cell Expansion in Severe Sepsis and Septic Shock

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