The Efficacy of Glutamine Supplementation in Severe Adult Burn Patients: A Systematic Review With Trial Sequential Meta-Analysis.

OBJECTIVES: Evidence supporting glutamine supplementation in severe adult burn patients has created a state of uncertainty due to the variability in the treatment effect reported across small and large randomized controlled trials (RCTs). We aimed to systematically review the effect of glutamine supplementation on mortality in severe adult burn patients. DATA SOURCES: MEDLINE, Embase, CINAHL, and Cochrane Central were searched from inception to February 10, 2023. STUDY SELECTION: RCTs evaluating the effect of enteral or IV glutamine supplementation alone in severe adult burn patients were included. DATA EXTRACTION: Two reviewers independently extracted data on study characteristics, burn injury characteristics, description of the intervention between groups, adverse events, and clinical outcomes. DATA SYNTHESIS: Random effects meta-analyses were performed to estimate the pooled risk ratio (RR). Trial sequential analyses (TSA) for mortality and infectious complications were performed. Ten RCTs (1,577 patients) were included. We observed no significant effect of glutamine supplementation on overall mortality (RR, 0.65, 95% CI, 0.33-1.28; p = 0.21), infectious complications (RR, 0.83; 95% CI, 0.63-1.09; p = 0.18), or other secondary outcomes. In subgroup analyses, we observed no significant effects based on administration route or burn severity. We did observe a significant subgroup effect between single and multicenter RCTs in which glutamine significantly reduced mortality and infectious complications in singe-center RCTs but not in multicenter RCTs. However, TSA showed that the pooled results of single-center RCTs were type 1 errors and further trials would be futile. CONCLUSIONS: Glutamine supplementation, regardless of administration, does not appear to improve clinical outcomes in severely adult burned patients.

Current practices in nutrition therapy in cardiac surgery patients: An international multicenter observational study.

BACKGROUND: Cardiac surgery patients with a prolonged stay in the intensive care unit (ICU) are at high risk for acquired malnutrition. Medical nutrition therapy practices for cardiac surgery patients are unknown. The objective of this study is to describe the current nutrition practices in critically ill cardiac surgery patients worldwide. METHODS: We conducted a prospective observational study in 13 international ICUs involving mechanically ventilated cardiac surgery patients with an ICU stay of at least 72 h. Collected data included the energy and protein prescription, type of and time to the initiation of nutrition, and actual quantity of energy and protein delivered (maximum: 12 days). RESULTS: Among 237 enrolled patients, enteral nutrition (EN) was started, on average, 45 h after ICU admission (range, 0-277 h; site average, 53 [range, 10-79 h]). EN was prescribed for 187 (79%) patients and combined EN and parenteral nutrition in 33 (14%). Overall, patients received 44.2% (0.0%-117.2%) of the prescribed energy and 39.7% (0.0%-122.8%) of the prescribed protein. At a site level, the average nutrition adequacy was 47.5% (30.5%-78.6%) for energy and 43.6% (21.7%-76.6%) for protein received from all nutrition sources. CONCLUSION: Critically ill cardiac surgery patients with prolonged ICU stay experience significant delays in starting EN and receive low levels of energy and protein. There exists tremendous variability in site performance, whereas achieving optimal nutrition performance is doable.

Case presentation and panel discussion: Micronutrient therapy in critical illness.

Over the past decade, the use of supraphysiologic doses of micronutrients (also called metabolic resuscitation) in critically ill patients has gained significant attention. Building upon preclinical and observational human data, numerous randomized controlled trials have tested the impact of multiple micronutrients on various outcomes in critically ill patients. At the 2022 American Society for Parenteral and Enteral Nutrition Preconference Course, three world-renowned speakers delivered talks on the (1) overall role of micronutrients and, specifically, (2) selenium and vitamin C and (3) vitamin D and zinc in critically ill patients. Here, the case presentation and discussion from the postsession question and answer period are presented. The moderator for this session was Jose Pimiento, MD, and the speakers and panelists were Christian Stoppe, MD, Todd Rice, MD, and Daren Heyland, MD.

Overview of oxidative stress and the role of micronutrients in critical illness.

Inflammation and oxidative stress represent physiological response mechanisms to different types of stimuli and injury during critical illness. Its proper regulation is fundamental to cellular and organismal survival and are paramount to outcomes and recovery from critical illness. A proper maintenance of the delicate balance between inflammation, oxidative stress, and immune response is crucial for resolution from critical illness with important implications for patient outcome. The extent of inflammation and oxidative stress under normal conditions is limited by the antioxidant defense system of the human body, whereas the antioxidant capacity is commonly significantly compromised, and serum levels of micronutrients and vitamins significantly depleted in patients who are critically ill. Hence, the provision of antioxidants and anti-inflammatory nutrients may help to reduce the extent of oxidative stress and therefore improve clinical outcomes in patients who are critically ill. As existing evidence of the beneficial effects of antioxidant supplementation in patients who are critically ill is still unclear, actual findings about the most promising anti-inflammatory and antioxidative candidates selenium, vitamin C, zinc, and vitamin D will be discussed in this narrative review. The existing evidence provided so far demonstrates that several factors need to be considered to determine the efficacy of an antioxidant supplementation strategy in patients who are critically ill and indicates the need for adequately designed multicenter prospective randomized control trials to evaluate the clinical significance of different types and doses of micronutrients and vitamins in selected groups of patients with different types of critical illness.

Medical nutrition therapy in patients receiving ECMO: Evidence-based guidance for clinical practice.

Patients receiving extracorporeal membrane oxygenation (ECMO) inherit substantial disease-associated metabolic, endocrinologic, and immunologic modifications. Along with the technical components of ECMO, the aforementioned alterations may affect patients' needs and feasibility of adequate macronutrient and micronutrient supply and intake. Thus, patients receiving ECMO are at increased risk for iatrogenic malnutrition and require targeted individual medical nutrition therapy (MNT). However, specific recommendations for MNT in patients receiving ECMO are limited and, with some exceptions, based on an evidence base encompassing general patients who are critically ill. Consequently, clinician decision-making for MNT in patients receiving ECMO is unguided, which may further increase nutrition risk, culminating in iatrogenic malnutrition and ultimately affecting patient outcomes. The purpose of this article is to provide educational background and highlight specific points for MNT in adult patients receiving ECMO, which might serve as evidence-based guidance to develop institutional standard operating procedures and nutrition protocols for daily clinical practice.

High-Dose IV Hydroxocobalamin (Vitamin B12) in Septic Shock: A Double-Blind, Allocation-Concealed, Placebo-Controlled Single-Center Pilot Randomized Controlled Trial (The Intravenous Hydroxocobalamin in Septic Shock Trial).

BACKGROUND: Elevated hydrogen sulfide (H2S) contributes to vasodilatation and hypotension in septic shock, and traditional therapies do not target this pathophysiologic mechanism. High-dose IV hydroxocobalamin scavenges and prevents H2S formation, which may restore vascular tone and may accentuate recovery. No experimental human studies have tested high-dose IV hydroxocobalamin in adults with septic shock. RESEARCH QUESTION: In adults with septic shock, is comparing high-dose IV hydroxocobalamin with placebo feasible? STUDY DESIGN AND METHODS: We conducted a phase 2 single-center, double-blind, allocation-concealed, placebo-controlled, parallel-group pilot randomized controlled trial comparing high-dose IV hydroxocobalamin with placebo in critically ill adults with septic shock. Patients meeting Sepsis 3 criteria were randomized 1:1 to receive a single 5-g dose of high-dose IV hydroxocobalamin or equivalent volume 0.9% saline solution as placebo. The primary outcome was study feasibility (enrollment rate, clinical and laboratory compliance rate, and contamination rate). Secondary outcomes included between-group differences in plasma H2S concentrations and vasopressor dose before and after infusion. RESULTS: Twenty patients were enrolled over 19 months, establishing an enrollment rate of 1.05 patients per month. Protocol adherence rates were 100% with zero contamination. In the high-dose IV hydroxocobalamin group, compared to placebo, there was a greater reduction in vasopressor dose between randomization and postinfusion (-36% vs 4%, P < .001) and randomization and 3-h postinfusion (-28% vs 10%, P = .019). In the high-dose IV hydroxocobalamin group, the plasma H2S level was reduced over 45 mins by -0.80 ± 1.73 µM, as compared with -0.21 ± 0.64 µM in the placebo group (P = .3). INTERPRETATION: This pilot trial established favorable feasibility metrics. Consistent with the proposed mechanism of benefit, high-dose IV hydroxocobalamin compared with placebo was associated with reduced vasopressor dose and H2S levels at all time points and without serious adverse events. These data provide the first proof of concept for feasibility of delivering high-dose IV hydroxocobalamin in septic shock. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT03783091; URL: www. CLINICALTRIALS: gov.

Optimizing the nutrition support care model: Analysis of survey data.

BACKGROUND: Malnutrition is underrecognized and underdiagnosed, despite high prevalence rates and associated poor clinical outcomes. The involvement of clinical nutrition experts, especially physicians, in the care of high-risk patients with malnutrition remains low despite evidence demonstrating lower complication rates with nutrition support team (NST) management. To facilitate solutions, a survey was designed to elucidate the nature of NSTs and physician involvement and identify needs for novel nutrition support care models. METHODS: This survey assessed demographics of NSTs, factors contributing to the success of NSTs, elements of nutrition education, and other barriers to professional growth. RESULTS: Of 255 respondents, 235 complete surveys were analyzed. The geographic distribution of respondents correlated with population concentrations of the United States (r = 90.8%, p < .0001). Most responding physicians (46/57; 80.7%) reported being a member of NSTs, compared with 56.5% (88/156) of dietitians. Of those not practicing in NSTs (N = 81/235, 34.4%), 12.3% (10/81) reported an NST was previously present at their institution but had been disbanded. Regarding NSTs, financial concerns were common (115/235; 48.9%), followed by leadership (72/235; 30.6%), and healthcare professional (HCP) interest (55/235; 23.4%). A majority (173/235; 73.6%) of all respondents wanted additional training in nutrition but reported insufficient protected time, ability to travel, or support from administrators or other HCPs. CONCLUSION: Core actions resulting from this survey focused on formalizing physician roles, increasing interdisciplinary nutrition support expertise, utilizing cost-effective screening for malnutrition, and implementing intervention protocols. Additional actions included increasing funding for clinical practice, education, and research, all within an expanded portfolio of pragmatic nutrition support care models.

IV Vitamin C in Critically Ill Patients: A Systematic Review and Meta-Analysis.

OBJECTIVES: To conduct a systematic review and meta-analysis to evaluate the impact of IV vitamin C on outcomes in critically ill patients. DATA SOURCES: Systematic search of MEDLINE, EMBASE, CINAHL, and the Cochrane Register of Controlled Trials. STUDY SELECTION: Randomized controlled trials testing IV vitamin C in critically ill patients. DATA ABSTRACTION: Two independent reviewers abstracted patient characteristics, treatment details, and clinical outcomes. DATA SYNTHESIS: Fifteen studies involving 2,490 patients were identified. Compared with placebo, IV vitamin C administration is associated with a trend toward reduced overall mortality (relative risk, 0.87; 95% CI, 0.75-1.00; p = 0.06; test for heterogeneity I2 = 6%). High-dose IV vitamin C was associated with a significant reduction in overall mortality (relative risk, 0.70; 95% CI, 0.52-0.96; p = 0.03), whereas low-dose IV vitamin C had no effect (relative risk, 0.94; 95% CI, 0.79-1.07; p = 0.46; test for subgroup differences, p = 0.14). IV vitamin C monotherapy was associated with a significant reduction in overall mortality (relative risk, 0.64; 95% CI, 0.49-0.83; p = 0.006), whereas there was no effect with IV vitamin C combined therapy. No trial reported an increase in adverse events related to IV vitamin C. CONCLUSIONS: IV vitamin C administration appears safe and may be associated with a trend toward reduction in overall mortality. High-dose IV vitamin C monotherapy may be associated with improved overall mortality, and further randomized controlled trials are warranted.

Barriers to nutrition therapy in the critically ill patient with COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has created challenges for intensivists, as high ventilatory demands and prolonged hypermetabolism make it difficult to sustain nutrition status. The purpose of this survey was to determine current practices in nutrition therapy and identify barriers to its delivery. METHODS: A survey about delivering nutrition therapy to critically ill patients with COVID-19 was sent to clinicians at academic and community hospitals from September to December 2020. RESULTS: Of 440 who viewed the survey, 199 (45%) completed the questionnaire. Respondents were composed of 30%, physicians and 70% registered dietitians, with 51% representing community programs, 43% academic institutions, and 6% Veterans Affairs centers. Half (49%) had protocols for managing critically ill patients with COVID-19, and 21% had a protocol for nutrition therapy. Although most respondents (83%) attempted to feed by the intragastric route, only 9% indicated that energy/protein needs were met. The biggest barriers to delivery of enteral nutrition (EN) involved the patients unpredictable clinical course and fear of aspiration given the lack of respiratory reserve. Intensivists were reluctant to add supplemental parenteral nutrition (PN) because of perceived lack of benefit. CONCLUSION: The survey results would suggest that strategies for nutrition therapy based on the intragastric infusion of EN are unsuccessful in meeting the energy/protein needs of critically ill patients with COVID-19. It is likely these barriers exist in providing nutrition to non-Covid-19 critically ill patients. Intensivists need protocols that optimally deliver intragastric EN, consider early postpyloric infusion, and address adding supplemental PN in a deteriorating nutrition status.

Guidelines for the provision of nutrition support therapy in the adult critically ill patient: The American Society for Parenteral and Enteral Nutrition.

BACKGROUND: This guideline updates recommendations from the 2016 American Society for Parenteral and Enteral Nutrition (ASPEN)/Society of Critical Care Medicine (SCCM) critical care nutrition guideline for five foundational questions central to critical care nutrition support. METHODS: The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) process was used to develop and summarize evidence for clinical practice recommendations. Clinical outcomes were assessed for (1) higher vs lower energy dose, (2) higher vs lower protein dose, (3) exclusive isocaloric parenteral nutrition (PN) vs enteral nutrition (EN), (4) supplemental PN (SPN) plus EN vs EN alone, (5A) mixed-oil lipid injectable emulsions (ILEs) vs soybean oil, and (5B) fish oil (FO)-containing ILE vs non-FO ILE. To assess safety, weight-based energy intake and protein were plotted against hospital mortality. RESULTS: Between January 1, 2001, and July 15, 2020, 2320 citations were identified and data were abstracted from 36 trials including 20,578 participants. Patients receiving FO had decreased pneumonia rates of uncertain clinical significance. Otherwise, there were no differences for any outcome in any question. Owing to a lack of certainty regarding harm, the energy prescription recommendation was decreased to 12-25 kcal/kg/day. CONCLUSION: No differences in clinical outcomes were identified among numerous nutrition interventions, including higher energy or protein intake, isocaloric PN or EN, SPN, or different ILEs. As more consistent critical care nutrition support data become available, more precise recommendations will be possible. In the meantime, clinical judgment and close monitoring are needed. This paper was approved by the ASPEN Board of Directors.

Relevant Nutrition Therapy in COVID-19 and the Constraints on Its Delivery by a Unique Disease Process.

Worldwide, as of July 2020, >13.2 million people have been infected by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. The spectrum of coronavirus disease 2019 (COVID-19) ranges from mild illness to critical illness in 5% of cases. The population infected with SARS-CoV-2 requiring an intensive care unit admission often requires nutrition therapy as part of supportive care. Although the various societal guidelines for critical care nutrition meet most needs for the patient with COVID-19, numerous factors, which impact the application of those guideline recommendations, need to be considered. Since the SARS-CoV-2 virus is highly contagious, several key principles should be considered when caring for all patients with COVID-19 to ensure the safety of all healthcare personnel involved. Management strategies should cluster care, making all attempts to bundle patient care to limit exposure. Healthcare providers should be protected, and the spread of SARS-CoV-2 should be limited by minimizing procedures and other interventions that lead to aerosolization, avoiding droplet exposure through hand hygiene and use of personal protective equipment (PPE). PPE should be preserved by decreasing the number of individuals providing direct patient care and by limiting the number of patient interactions. Enteral nutrition (EN) is tolerated by the majority of patients with COVID-19, but a relatively low threshold for conversion to parenteral nutrition should be maintained if increased exposure to the virus is required to continue EN. This article offers relevant and practical recommendations on how to optimize nutrition therapy in critically ill patients with COVID-19.

Nutrition Therapy in Critically Ill Patients With Coronavirus Disease 2019.

In the midst of a coronavirus disease 2019 (COVID-19) pandemic, a paucity of data precludes derivation of COVID-19-specific recommendations for nutrition therapy. Until more data are available, focus must be centered on principles of critical care nutrition modified for the constraints of this disease process, ie, COVID-19-relevant recommendations. Delivery of nutrition therapy must include strategies to reduce exposure and spread of disease by providing clustered care, adequate protection of healthcare providers, and preservation of personal protective equipment. Enteral nutrition (EN) should be initiated early after admission to the intensive care unit (ICU) using a standard isosmolar polymeric formula, starting at trophic doses and advancing as tolerated, while monitoring for gastrointestinal intolerance, hemodynamic instability, and metabolic derangements. Intragastric EN may be provided safely, even with use of prone-positioning and extracorporeal membrane oxygenation. Clinicians should have a lower threshold for switching to parenteral nutrition in cases of intolerance, high risk of aspiration, or escalating vasopressor support. Although data extrapolated from experience in acute respiratory distress syndrome warrants use of fiber additives and probiotic organisms, the lack of benefit precludes a recommendation for micronutrient supplementation. Practices that increase exposure or contamination of equipment, such as monitoring gastric residual volumes, indirect calorimetry to calculate requirements, endoscopy or fluoroscopy to achieve enteral access, or transport out of the ICU for additional imaging, should be avoided. At all times, strategies for nutrition therapy need to be assessed on a risk/benefit basis, paying attention to risk for both the patient and the healthcare provider.

High-Dose Vitamin B12 in Vasodilatory Shock: A Narrative Review.

Vasodilatory shock, as observed in postoperative states and sepsis, is hallmarked by low systemic vascular resistance and low blood pressure compensated by increased cardiac output. Gasotransmitters, such as nitric oxide and hydrogen sulfide, are implicated in the development and perpetuation of vasodilatory shock. Established therapies do not target these physiologic drivers of vasodilation. Due to their nontoxic and pleotropic effects, micronutrients are being used as rescue therapy in postoperative vasoplegia and septic shock. Here, we outline the pathophysiology of vasodilatory shock, describe the rationale for vitamin B12 (hydroxocobalamin) in vasodilatory shock, and identify literature evaluating its use in vasoplegic states.

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

PURPOSE OF THE REVIEW: Fish 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 FINDINGS: Thereafter, 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). This 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.

Barriers and Solutions to Delivery of Intensive Care Unit Nutrition Therapy.

Despite recommendations for early enteral nutrition (EN) in critically ill patients, numerous factors contribute to incomplete delivery of EN, including insufficient nutrition risk screening in critically ill patients, underutilization of enteral feeding protocols, fixed rate-based enteral infusion targets with frequent EN interruption, and suboptimal provider practices regarding nutrition support therapy. The purpose of this narrative review is to identify common barriers to optimizing and delivering nutrition in critically ill patients, and suggest strategies and solutions to overcome barriers.

Controversies Surrounding Critical Care Nutrition: An Appraisal of Permissive Underfeeding, Protein, and Outcomes.

Over the past few years, numerous studies have called into question the optimal dose, timing, composition, and advancement rate of nutrition during the early acute phase of critical illness. These studies suggest permissive underfeeding with slow advancement may be more beneficial than aggressive full feeding. These counterintuitive results were possibly explained by enhanced autophagy, less hyperglycemia, or prevention of refeeding syndrome. This review underscores the controversies surrounding permissive underfeeding, aims to answer whether permissive underfeeding is appropriate for all critically ill patients, describes the impact of optimal protein delivery on critical care outcomes, discusses nutrition risk, and cogitates on the impact of nutrition on critical care outcomes.

Protein Kinetics and Metabolic Effects Related to Disease States in the Intensive Care Unit.

Evaluating protein kinetics in the critically ill population remains a very difficult task. Heterogeneity in the intensive care unit (ICU) population and wide spectrum of disease processes creates complexity in assessing protein kinetics. Traditionally, protein has been delivered in the context of total energy. Focus on energy delivery has recently come into question, as the importance of supplemental protein in patient outcomes has been shown in several recent trials. The ICU patient is prone to catabolism, immobilization, and impaired immunity, which is a perfect storm for massive loss of lean body tissue with a unidirectional flow of amino acids from muscle to immune tissue for immunoglobulin production, as well as liver for gluconeogenesis and acute phase protein synthesis. The understanding of protein metabolism in the ICU has been recently expanded with the discovery of how the mammalian target of rapamycin complex 1 is regulated. The concept of "anabolic resistance" and identifying the quantity of protein required to overcome this resistance is gaining support among critical care nutrition circles. It appears that a minimum of at least 1.2 g/kg/d with levels up to 2.0 g/kg/d of protein or amino acids appears safe for delivery in the ICU setting and may yield a better clinical outcome.

Critical Care Nutrition: Where's the Evidence?

The surgical critically ill patient is subject to a variable and complex metabolic response, which has detrimental effects on immunity, wound healing, and preservation of lean body muscle. The concept of nutrition support has evolved into nutrition therapy, whereby the primary objectives are to prevent oxidative cell injury, modulate the immune response, and attenuate the metabolic response. This review outlines the metabolic response to critical illness, describes nutritional risk; reviews the evidence for the role, dose, and timing of enteral and parenteral nutrition, and reviews the evidence for immunonutrition in the surgical intensive care unit.