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.

History of scurvy and use of vitamin C in critical illness: A narrative review.

In 1747, an important milestone in the history of clinical research was set, as the Scottish surgeon James Lind conducted the first randomized controlled trial. Lind was interested in scurvy, a severe vitamin C deficiency which caused the death of thousands of British seamen. He found that a dietary intervention with oranges and lemons, which are rich in vitamin C by nature, was effective to recover from scurvy. Because of its antioxidative properties and involvement in many biochemical processes, the essential micronutrient vitamin C plays a key role in the human biology. Moreover, the use of vitamin C in critical illness-a condition also resulting in death of thousands in the 21st century-has gained increasing interest, as it may restore vascular responsiveness to vasoactive agents, ameliorate microcirculatory blood flow, preserve endothelial barriers, augment bacterial defense, and prevent apoptosis. Because of its redox potential and powerful antioxidant capacity, vitamin C represents an inexpensive and safe antioxidant, with the potential to modify the inflammatory cascade and improve clinical outcomes of critically ill patients. This narrative review aims to update and provide an overview on the role of vitamin C in the human biology and in critically ill patients, and to summarize current evidence on the use of vitamin C in diverse populations of critically ill patients, in specific focusing on patients with sepsis and coronavirus disease 2019.

The effect of higher versus lower protein delivery in critically ill patients: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The optimal protein dose in critical illness is unknown. We aim to conduct a systematic review of randomized controlled trials (RCTs) to compare the effect of higher versus lower protein delivery (with similar energy delivery between groups) on clinical and patient-centered outcomes in critically ill patients. METHODS: We searched MEDLINE, EMBASE, CENTRAL and CINAHL from database inception through April 1, 2021.We included RCTs of (1) adult (age ≥ 18) critically ill patients that (2) compared higher vs lower protein with (3) similar energy intake between groups, and (4) reported clinical and/or patient-centered outcomes. We excluded studies on immunonutrition. Two authors screened and conducted quality assessment independently and in duplicate. Random-effect meta-analyses were conducted to estimate the pooled risk ratio (dichotomized outcomes) or mean difference (continuous outcomes). RESULTS: Nineteen RCTs were included (n = 1731). Sixteen studies used primarily the enteral route to deliver protein. Intervention was started within 72 h of ICU admission in sixteen studies. The intervention lasted between 3 and 28 days. In 11 studies that reported weight-based nutrition delivery, the pooled mean protein and energy received in higher and lower protein groups were 1.31 ± 0.48 vs 0.90 ± 0.30 g/kg and 19.9 ± 6.9 versus 20.1 ± 7.1 kcal/kg, respectively. Higher vs lower protein did not significantly affect overall mortality [risk ratio 0.91, 95% confidence interval (CI) 0.75-1.10, p = 0.34] or other clinical or patient-centered outcomes. In 5 small studies, higher protein significantly attenuated muscle loss (MD -3.44% per week, 95% CI -4.99 to -1.90; p < 0.0001). CONCLUSION: In critically ill patients, a higher daily protein delivery was not associated with any improvement in clinical or patient-centered outcomes. Larger, and more definitive RCTs are needed to confirm the effect of muscle loss attenuation associated with higher protein delivery. PROSPERO registration number: CRD42021237530.

Case presentation and panel discussion: Critical illness.

Despite a mounting evidentiary base, controversies surrounding critical care nutrition support persist. Anchored by a case of a 60-year-old male with esophageal cancer who develops acute hypoxemic respiratory failure and septic shock, five panelists from the American Society of Parenteral and Enteral Nutrition (ASPEN) 2021 Pre-Conference discuss key clinical dilemmas in critical care nutrition, including hierarchy of evidence, bedside evaluation of malnutrition, optimal protein dose, use of fiber, and therapies targeting gut function and gut microbiota .

Case presentation and panel discussion: Nutrition issues in cancer.

Advances in treatment of malignancy including novel pharmacologic therapies and surgical interventions has led to significant improvement in survival. As cancer becomes a chronic disease, nutrition interventions play an increasingly important role in short- and long-term outcomes. The current manuscript presents a case of a 66-year-old male with new diagnosis of pancreatic cancer diagnosed incidentally in the setting of COVID-19. Expert panelists in the field of nutrition discuss optimal strategies for diagnosis of malnutrition along with preoperative, perioperative, and postoperative optimization of nutrition. This discussion focuses on the use of probiotics, immune-modulating nutrition, fish oil, specialized proresolving mediators, and use of enteral and parenteral nutrition support.

When Pandemics Collide: the Interplay of Obesity and COVID-19.

PURPOSE OF REVIEW: The COVID-19 pandemic has been associated with significant morbidity and mortality worldwide. In addition to those with advanced age and co-morbidities such as heart disease or cancer, obese individuals have also had very high rates of hospitalization, critical illness, need for ventilator support, as well as mortality. A number of factors associated with obesity have led to devastating consequences as these two pandemics have interacted. RECENT FINDINGS: Obese individuals through a combination of structural and cellular level changes have greater risk of ischemic heart disease, diabetes, cancer, and respiratory disease, which are themselves risk-factors for acquiring COVID-19 disease. These structural changes also result in increased intra-abdominal and intra-thoracic pressure as well as a restrictive lung physiology that leads to reduction in total lung capacity, functional residual capacity, and increase in airway hyper-reactivity. Adipose tissue is also impacted in obese individuals leading to local as well as systemic inflammation, which can contribute to increased release of free fatty acids and systemic insulin resistance. Additionally, angiotensin-converting enzyme 2 and dipeptidyl peptidase 4, which act as receptors for SARS-CoV-2 are also significantly increased in obese individuals. The present manuscript reviews these structural, immune, and molecular changes associated with obesity that make obese individuals more vulnerable to acquiring severe COVID-19 and more challenging to manage associated complications.

Clinical Nutrition Research and the COVID-19 Pandemic: A Scoping Review of the ASPEN COVID-19 Task Force on Nutrition Research.

The purpose of this scoping review by the American Society for Parenteral and Enteral Nutrition (ASPEN) Coronavirus Disease 2019 (COVID-19) Nutrition Task Force was to examine nutrition research applicable to the COVID-19 pandemic. The rapid pace of emerging scientific information has prompted this activity to discover research/knowledge gaps. This methodology adhered with recommendations from the Joanna Briggs Institute. There were 2301 citations imported. Of these, there were 439 articles fully abstracted, with 23 main topic areas identified across 24 article types and sourced across 61 countries and 51 specialties in 8 settings and among 14 populations. Epidemiological/mechanistic relationships between nutrition and COVID-19 were reviewed and results mapped to the Population, Intervention, Comparator, Outcome, and Time (PICO-T) questions. The aggregated data were analyzed by clinical stage: pre-COVID-19, acute COVID-19, and chronic/post-COVID-19. Research gaps were discovered for all PICO-T questions. Nutrition topics meriting urgent research included food insecurity/societal infrastructure and transcultural factors (pre-COVID-19); cardiometabolic-based chronic disease, pediatrics, nutrition support, and hospital infrastructure (acute COVID-19); registered dietitian nutritionist counseling (chronic/post-COVID-19); and malnutrition and management (all stages). The paucity of randomized controlled trials (RCTs) was particularly glaring. Knowledge gaps were discovered for PICO-T questions on pediatrics, micronutrients, bariatric surgery, and transcultural factors (pre-COVID-19); enteral nutrition, protein-energy requirements, and glycemic control with nutrition (acute COVID-19); and home enteral and parenteral nutrition support (chronic/post-COVID-19). In conclusion, multiple critical areas for urgent nutrition research were identified, particularly using RCT design, to improve nutrition care for patients before, during, and after 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.

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.