-
1.
Clinical Significance of Micronutrient Supplementation in Critically Ill COVID-19 Patients with Severe ARDS.
Notz, Q, Herrmann, J, Schlesinger, T, Helmer, P, Sudowe, S, Sun, Q, Hackler, J, Roeder, D, Lotz, C, Meybohm, P, et al
Nutrients. 2021;(6)
Abstract
The interplay between inflammation and oxidative stress is a vicious circle, potentially resulting in organ damage. Essential micronutrients such as selenium (Se) and zinc (Zn) support anti-oxidative defense systems and are commonly depleted in severe disease. This single-center retrospective study investigated micronutrient levels under Se and Zn supplementation in critically ill patients with COVID-19 induced acute respiratory distress syndrome (ARDS) and explored potential relationships with immunological and clinical parameters. According to intensive care unit (ICU) standard operating procedures, patients received 1.0 mg of intravenous Se daily on top of artificial nutrition, which contained various amounts of Se and Zn. Micronutrients, inflammatory cytokines, lymphocyte subsets and clinical data were extracted from the patient data management system on admission and after 10 to 14 days of treatment. Forty-six patients were screened for eligibility and 22 patients were included in the study. Twenty-one patients (95%) suffered from severe ARDS and 14 patients (64%) survived to ICU discharge. On admission, the majority of patients had low Se status biomarkers and Zn levels, along with elevated inflammatory parameters. Se supplementation significantly elevated Se (p = 0.027) and selenoprotein P levels (SELENOP; p = 0.016) to normal range. Accordingly, glutathione peroxidase 3 (GPx3) activity increased over time (p = 0.021). Se biomarkers, most notably SELENOP, were inversely correlated with CRP (rs = -0.495), PCT (rs = -0.413), IL-6 (rs = -0.429), IL-1β (rs = -0.440) and IL-10 (rs = -0.461). Positive associations were found for CD8+ T cells (rs = 0.636), NK cells (rs = 0.772), total IgG (rs = 0.493) and PaO2/FiO2 ratios (rs = 0.504). In addition, survivors tended to have higher Se levels after 10 to 14 days compared to non-survivors (p = 0.075). Sufficient Se and Zn levels may potentially be of clinical significance for an adequate immune response in critically ill patients with severe COVID-19 ARDS.
-
2.
Nutrition in Sepsis: A Bench-to-Bedside Review.
De Waele, E, Malbrain, MLNG, Spapen, H
Nutrients. 2020;(2)
Abstract
Nutrition therapy in sepsis is challenging and differs from the standard feeding approach in critically ill patients. The dysregulated host response caused by infection induces progressive physiologic alterations, which may limit metabolic capacity by impairing mitochondrial function. Hence, early artificial nutrition should be ramped-up and emphasis laid on the post-acute phase of critical illness. Caloric dosing is ideally guided by indirect calorimetry, and endogenous energy production should be considered. Proteins should initially be delivered at low volume and progressively increased to 1.3 g/kg/day following shock symptoms wane. Both the enteral and parenteral route can be (simultaneously) used to cover caloric and protein targets. Regarding pharmaconutrition, a low dose glutamine seems appropriate in patients receiving parenteral nutrition. Supplementing arginine or selenium is not recommended. High-dose vitamin C administration may offer substantial benefit, but actual evidence is too limited for advocating its routine use in sepsis. Omega-3 polyunsaturated fatty acids to modulate metabolic processes can be safely used, but non-inferiority to other intravenous lipid emulsions remains unproven in septic patients. Nutrition stewardship, defined as the whole of interventions to optimize nutritional approach and treatment, should be pursued in all septic patients but may be difficult to accomplish within a context of profoundly altered cellular metabolic processes and organ dysfunction caused by time-bound excessive inflammation and/or immune suppression. This review aims to provide an overview and practical recommendations of all aspects of nutritional therapy in the setting of sepsis.
-
3.
Hypovitaminosis C and vitamin C deficiency in critically ill patients despite recommended enteral and parenteral intakes.
Carr, AC, Rosengrave, PC, Bayer, S, Chambers, S, Mehrtens, J, Shaw, GM
Critical care (London, England). 2017;(1):300
Abstract
BACKGROUND Vitamin C is an essential water-soluble nutrient which cannot be synthesised or stored by humans. It is a potent antioxidant with anti-inflammatory and immune-supportive roles. Previous research has indicated that vitamin C levels are depleted in critically ill patients. In this study we have assessed plasma vitamin C concentrations in critically ill patients relative to infection status (septic shock or non-septic) and level of inflammation (C-reactive protein concentrations). Vitamin C status was also assessed relative to daily enteral and parenteral intakes to determine if standard intensive care unit (ICU) nutritional support is adequate to meet the vitamin C needs of critically ill patients. METHODS Forty-four critically ill patients (24 with septic shock, 17 non-septic, 3 uncategorised) were recruited from the Christchurch Hospital Intensive Care Unit. We measured concentrations of plasma vitamin C and a pro-inflammatory biomarker (C-reactive protein) daily over 4 days and calculated patients' daily vitamin C intake from the enteral or total parenteral nutrition they received. We compared plasma vitamin C and C-reactive protein concentrations between septic shock and non-septic patients over 4 days using a mixed effects statistical model, and we compared the vitamin C status of the critically ill patients with known vitamin C bioavailability data using a four-parameter log-logistic response model. RESULTS Overall, the critically ill patients exhibited hypovitaminosis C (i.e., < 23 μmol/L), with a mean plasma vitamin C concentration of 17.8 ± 8.7 μmol/L; of these, one-third had vitamin C deficiency (i.e., < 11 μmol/L). Patients with hypovitaminosis C had elevated inflammation (C-reactive protein levels; P < 0.05). The patients with septic shock had lower vitamin C concentrations and higher C-reactive protein concentrations than the non-septic patients (P < 0.05). Nearly 40% of the septic shock patients were deficient in vitamin C, compared with 25% of the non-septic patients. These low vitamin C levels were apparent despite receiving recommended intakes via enteral and/or parenteral nutritional therapy (mean 125 mg/d). CONCLUSIONS Critically ill patients have low vitamin C concentrations despite receiving standard ICU nutrition. Septic shock patients have significantly depleted vitamin C levels compared with non-septic patients, likely resulting from increased metabolism due to the enhanced inflammatory response observed in septic shock.
-
4.
Intestinal T lymphocyte homing is associated with gastric emptying and epithelial barrier function in critically ill: a prospective observational study.
Greis, C, Rasuly, Z, Janosi, RA, Kordelas, L, Beelen, DW, Liebregts, T
Critical care (London, England). 2017;(1):70
Abstract
BACKGROUND Impaired gastric emptying is common in critically ill patients. Intestinal dysmotility, a major cause of feed intolerance, may foster infectious complications due to mucosal barrier disruption. However, little is known about gut-directed immune activation, intestinal barrier function and its association with impaired gastric emptying in critically ill patients at ICU admission. METHODS We conducted a prospective observational study at two tertiary care medical ICUs. Fifty consecutive patients needing invasive mechanical ventilation were recruited within 24 h of ICU admission, prior to any nutritional support. The acute physiology and chronic health evaluation (APACHE) II score, the sequential organ failure assessment (SOFA) score and the multiple organ dysfunction score (MODS) were used to assess illness severity and multiple organ dysfunction. Gastric emptying was assessed by paracetamol absorption test. Peripheral blood mononuclear cells were freshly isolated and cultured for 24 h, and TNF-α, IL-1β and IL-10 measured in cell culture supernatants and in serum by ELISA. The intestinal epithelial barrier was assessed, quantifying serum concentrations of intestinal fatty acid binding protein (I-FABP), ileal bile-acid binding protein (I-BABP) and zonulin-1 by ELISA. Small bowel homing T lymphocytes (CD4+ α4β7 + CCR9+) were analyzed by flow cytometry. The Mann-Whitney test and Spearman correlation were used in statistical evaluation. RESULTS CD4 + α4β7 + CCR9+ T lymphocytes were inversely correlated with gastric emptying. Patients with delayed gastric emptying at ICU admission (n = 35) had significantly higher serum and PBMC-induced TNF-α and IL-1β and increased intestinal barrier disruption reflected by higher I-FABP, I-BABP and zonulin-1. Patients who died in the ICU had significantly impaired gastric empting at admission compared to ICU survivors. No differences were observed in APACHE II, SOFA or MODS in patients with delayed gastric emptying compared to patients with normal gastric emptying. CONCLUSIONS Exaggerated CD4 + α4β7 + CCR9+ T lymphocyte homing with increased pro-inflammatory cytokine release and intestinal epithelial barrier disruption are associated with delayed gastric emptying. This is not simply due to differences in overall severity of illness at ICU admission and may represent a pathophysiological mechanism of gut-directed immune activation leading to impaired barrier function in the critically ill.
-
5.
Interaction Between 2 Nutraceutical Treatments and Host Immune Status in the Pediatric Critical Illness Stress-Induced Immune Suppression Comparative Effectiveness Trial.
Carcillo, JA, Dean, JM, Holubkov, R, Berger, J, Meert, KL, Anand, KJS, Zimmerman, JJ, Newth, CJL, Harrison, R, Burr, J, et al
JPEN. Journal of parenteral and enteral nutrition. 2017;(8):1325-1335
-
-
Free full text
-
Abstract
BACKGROUND AND AIMS The pediatric Critical Illness Stress-induced Immune Suppression (CRISIS) trial compared the effectiveness of 2 nutraceutical supplementation strategies and found no difference in the development of nosocomial infection and sepsis in the overall population. We performed an exploratory post hoc analysis of interaction between nutraceutical treatments and host immune status related to the development of nosocomial infection/sepsis. METHODS Children from the CRISIS trial were analyzed according to 3 admission immune status categories marked by decreasing immune competence: immune competent without lymphopenia, immune competent with lymphopenia, and previously immunocompromised. The comparative effectiveness of the 2 treatments was analyzed for interaction with immune status category. RESULTS There were 134 immune-competent children without lymphopenia, 79 previously immune-competent children with lymphopenia, and 27 immunocompromised children who received 1 of the 2 treatments. A significant interaction was found between treatment arms and immune status on the time to development of nosocomial infection and sepsis ( P < .05) and on the rate of nosocomial infection and sepsis per 100 patient days ( P < .05). Whey protein treatment protected immune-competent patients without lymphopenia from infection and sepsis, both nutraceutical strategies were equivalent in immune-competent patients with lymphopenia, and zinc, selenium, glutamine, and metoclopramide treatment protected immunocompromised patients from infection and sepsis. CONCLUSIONS The science of immune nutrition is more complex than previously thought. Future trial design should consider immune status at the time of trial entry because differential effects of nutraceuticals may be related to this patient characteristic.
-
6.
Vitamin D in critically ill patients.
Matysiak-Luśnia, K
Anaesthesiology intensive therapy. 2016;(3):201-7
Abstract
Vitamin D deficiency is a commonly observed global phenomenon, both in the general population and in hospitalized patients, including critically ill patients. Vitamin D deficiency is associated with multiple adverse health outcomes, including increased morbidity and mortality in the general population and in critically ill patients. Vitamin D is a fatsoluble vitamin that plays an important role in bone metabolism. However, Vitamin D is also a steroid hormone that exerts multiple pleiotropic effects. Vitamin D regulates immunity, inflammation, cell proliferation, differentiation, apoptosis, and angiogenesis. There is growing evidence of a close relationship between vitamin D insufficiency and various systemic disorders, i.e., type II diabetes, certain types of cancer, obesity, and cardiovascular morbidities. The purpose of this article is to present the current knowledge on the relationship between vitamin D status and critical illness.
-
7.
Efficacy of probiotic therapy in full-term infants with critical illness.
Wang, Y, Gao, L, Zhang, YH, Shi, CS, Ren, CM
Asia Pacific journal of clinical nutrition. 2014;(4):575-80
Abstract
BACKGROUND Probiotics are microbial supplements that have shown efficacy in a wide range of applications. To assess the safety and effects of enteral probiotics in critically ill neonates. METHODS A double-blind, randomized controlled trial was conducted in 100 full-term infants with critical illness according to scores of neonatal acute physiology. Fifty neonatal intensive care patients were randomly assigned to receive probiotics three times daily after birth for 8 days, and fifty patients were not given probiotics, but who received a placebo. The incidence of sepsis, multiple organ dysfunction syndrome (MODS), nosocomial pneumonia, and necrotizing enterocolitis were recorded. The prognosis of probiotic treatment was determined based on the rate of recovery and hospital days. Serum IgA, IgG, and IgM concentrations were measured on days 4 and 8. RESULTS Infants in the probiotics group showed a significantly reduced rate of nosocomial pneumonia (18% versus 36%) and multiple organ dysfunction syndrome (6% versus 16%) compared with the placebo group (p<0.05). Significant results were demonstrated in favour of the probiotics for days of hospital stay (13 ± 3.5 d versus 15.8 ± 5.3 d) (p<0.05). However, there were no significant differences in the occurrence of sepsis, necrotizing enterocolitis, and recovery rate. Patients given probiotics had significantly greater levels of IgA than those in the placebo group (p<0.05). No serious adverse effects in the study population were noted. CONCLUSIONS Supplements of probiotics to critically ill neonates could enhance immune activity, decrease occurrence of nosocomial pneumonia and MODS, and reduce days in hospital.
-
8.
Probiotic/synbiotic therapy for treating critically ill patients from a gut microbiota perspective.
Shimizu, K, Ogura, H, Asahara, T, Nomoto, K, Morotomi, M, Tasaki, O, Matsushima, A, Kuwagata, Y, Shimazu, T, Sugimoto, H
Digestive diseases and sciences. 2013;(1):23-32
-
-
Free full text
-
Abstract
The gut is an important target organ for stress caused by severe insults such as sepsis, trauma, burn, shock, bleeding and infection. Severe insult to the gut is considered to have an important role in promoting infectious complications and multiple organ dysfunction syndrome. These are sequelae of interactions between deteriorated intestinal epithelium, the immune system and commensal bacteria. The gut is the "motor" of multiple organ failure, and now it is recognized that gut dysfunction is a causative factor in disease progression. The gut flora and environment are significantly altered in critically ill patients, and the number of obligate anaerobes is associated with prognosis. Synbiotic therapy is a combination of probiotics and prebiotics. Probiotic, prebiotic and synbiotic treatment has been shown to be a promising therapy to maintain and repair the gut microbiota and gut environment. In the critically ill, such as major abdominal surgery, trauma and ICU patients, synbiotic therapy has been shown to significantly reduce septic complications. Further basic and clinical research would clarify the underlying mechanisms of the therapeutic effect of probiotic/synbiotic treatment and define the appropriate conditions for use.
-
9.
The randomized comparative pediatric critical illness stress-induced immune suppression (CRISIS) prevention trial.
Carcillo, JA, Dean, JM, Holubkov, R, Berger, J, Meert, KL, Anand, KJ, Zimmerman, J, Newth, CJ, Harrison, R, Burr, J, et al
Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies. 2012;(2):165-73
-
-
Free full text
-
Abstract
OBJECTIVES Nosocomial infection/sepsis occurs in up to 40% of children requiring long-term intensive care. Zinc, selenium, glutamine, metoclopramide (a prolactin secretalogue), and/or whey protein supplementation have been effective in reducing infection and sepsis in other populations. We evaluated whether daily nutriceutical supplementation with zinc, selenium, glutamine, and metoclopramide, compared to whey protein, would reduce the occurrence of nosocomial infection/sepsis in this at-risk population. DESIGN Randomized, double-blinded, comparative effectiveness trial. SETTING Eight pediatric intensive care units in the National Institutes of Child Health and Human Development Collaborative Pediatric Critical Care Research Network. PATIENTS Two hundred ninety-three long-term intensive care patients (age 1-17 yrs) expected to require >72 hrs of invasive care. INTERVENTIONS Patients were stratified according to immunocompromised status and center and then were randomly assigned to receive daily enteral zinc, selenium, glutamine, and intravenous metoclopramide (n = 149), or daily enteral whey protein (n = 144) and intravenous saline for up to 28 days of intensive care unit stay. The primary end point was time to development of nosocomial sepsis/infection. The analysis was intention to treat. MEASUREMENTS AND MAIN RESULTS There were no differences by assigned treatment in the overall population with respect to time until the first episode of nosocomial infection/sepsis (median whey protein 13.2 days vs. zinc, selenium, glutamine, and intravenous metoclopramide 12.1 days; p = .29 by log-rank test) or the rate of nosocomial infection/sepsis (4.83/100 days whey protein vs. 4.99/100 days zinc, selenium, glutamine, and intravenous metoclopramide; p = .81). Only 9% of the 293 subjects were immunocompromised and there was a reduction in rate of nosocomial infection/sepsis with zinc, selenium, glutamine, and intravenous metoclopramide in this immunocompromised group (6.09/100 days whey protein vs. 1.57/100 days zinc, selenium, glutamine, and intravenous metoclopramide; p = .011). CONCLUSION Compared with whey protein supplementation, zinc, selenium, glutamine, and intravenous metoclopramide conferred no advantage in the immune-competent population. Further evaluation of zinc, selenium, glutamine, and intravenous metoclopramide supplementation is warranted in the immunocompromised long-term pediatric intensive care unit patient.
-
10.
Clinical review: Optimizing enteral nutrition for critically ill patients--a simple data-driven formula.
Hegazi, RA, Wischmeyer, PE
Critical care (London, England). 2011;(6):234
Abstract
In modern critical care, the paradigm of 'therapeutic nutrition' is replacing traditional 'supportive nutrition'. Standard enteral formulas meet basic macro- and micronutrient needs; therapeutic enteral formulas meet these basic needs and also contain specific pharmaconutrients that may attenuate hyperinflammatory responses, enhance the immune responses to infection, or improve gastrointestinal tolerance. Choosing the right enteral feeding formula may positively affect a patient's outcome; targeted use of therapeutic formulas can reduce the incidence of infectious complications, shorten lengths of stay in the ICU and in the hospital, and lower risk for mortality. In this paper, we review principles of how to feed (enteral, parenteral, or both) and when to feed (early versus delayed start) patients who are critically ill. We discuss what to feed these patients in the context of specific pharmaconutrients in specialized feeding formulations, that is, arginine, glutamine, antioxidants, certain ω-3 and ω-6 fatty acids, hydrolyzed proteins, and medium-chain triglycerides. We summarize current expert guidelines for nutrition in patients with critical illness, and we present specific clinical evidence on the use of enteral formulas supplemented with anti-inflammatory or immune-modulating nutrients, and gastrointestinal tolerance-promoting nutritional formulas. Finally, we introduce an algorithm to help bedside clinicians make data-driven feeding decisions for patients with critical illness.