Acute Phase Of Critical Illness Research Articles

Metabolism of Proteins and Amino Acids in Critical Illness: From Physiological Alterations to Relevant Clinical Practice.

The clinical impact of nutrition therapy in critically ill patients has been known for years, and relevant guidelines regarding nutrition therapy have emphasized the importance of proteins. During critical illness, such as sepsis or the state following major surgery, major trauma, or major burn injury, patients suffer from a high degree of stress/inflammation, and during this time, metabolism deviates from homeostasis. The increased degradation of endogenous proteins in response to stress hormones is among the most important events in the acute phase of critical illness. Currently published evidence suggests that adequate protein supplementation might improve the clinical outcomes of critically ill patients. The role of sufficient protein supplementation may even surpass that of caloric supplementation. In this review, we focus on relevant physiological alterations in critical illness, the effects of critical illness on protein metabolism, nutrition therapy in clinical practice, and the function of specific amino acids.

Chapter 29 - Endocrine interventions in the intensive care unit

Following the onset of any life-threatening illness that requires intensive medical care, alterations within the neuroendocrine axes occur which are thought to be essential for survival, as they postpone energy-consuming anabolism, activate energy-producing catabolic pathways, and optimize immunological and cardiovascular functions. The hormonal changes present in the acute phase of critical illness at least partially resemble those of the fasting state, and recent evidence suggests that they are part of a beneficial, evolutionary-conserved adaptive stress response. However, a fraction of patients who survive the acute phase of critical illness remain dependent on vital organ support and enter the prolonged phase of critical illness. In these patients, the hypothalamic-pituitary-peripheral axes are functionally suppressed, which may have negative consequences by which recovery may be hampered and the risk of morbidity and mortality in the long-term increased. Most randomized controlled trials of critically ill patients that investigated the impact on the outcome of treatment with peripheral hormones did not reveal a robust morbidity or mortality benefit. In contrast, small studies of patients in the prolonged phase of critical illness documented promising results with the infusion of hypothalamic-releasing hormones. The currently available data corroborate the need for well-designed and adequately powered RCTs to further investigate the impact of these releasing factors on patient-centered outcomes.

Challenges to delivering family‐centred care during the Coronavirus pandemic: Voices of Italian paediatric intensive care unit nurses

Challenges to delivering family‐centred care during the Coronavirus pandemic: Voices of Italian paediatric intensive care unit nurses

O futuro da nutrição parenteral no paciente crítico

Gastrointestinal dysfunction and inadequate nutrient intake are frequently seen in critically ill patients. Recent studies have shown that parenteral nutrition is safe among these patients. This narrative review aims to describe the risks associated with overfeeding and how to safely indicate and implement parenteral nutrition in the intensive care unit. After the acute phase of critical illness, individualized parenteral nutrition, using indirect calorimetry and balanced lipid emulsions, may be associated with better outcomes. The demand for ready-to-use bags has been growing intended to achieve the best value of care for patients and healthcare institutions.

ULTRASOUND MONITORING OF MUSCLE MASS CHANGES FOR TARGETING OF NUTRITIONAL SUPPORT IN NEUROCRITICALLY ILL PATIENTS

The main goal of this study was to identify a way to optimize nutritional support during ICU stay and obtain information about catabolic state through non-invasive and reliable methods as ultrasonography. We designed an observational case-series of 11 critically ill patients hospitalised at NEURO-ICU at IRCCS Bellaria Hospital - Bologna. The population studied shown uniform characteristics wich allowed comparison for muscle mass changes. Primary endpoint was to evaluate ultrasound sensitivity for monitoring muscle mass changes considering muscle layer thickness. Secondarly we compared ultrasonographic data and biomarkers of catabolism (sCr, nitrogen balance) in order to assess correlation between nutritional intakes (calories and protein) and changes in muscle during monitoring range of time. According to statistical index (CV<5%, ICC and Lin's Coefficient) the best reliable muscles for ultrasound monitoring resulted Rectus Femoris (RF), Vastus Intermedius (VI) and Tibialis Anterior (TA). The most statistically relevant (p<0.05) reduction of muscle layer thickness happened between Day1 and Day14 for Right VI, Right and Left TA. Significant correlation between APACHE II scored within first 24 hours of ICU admission emerged with muscle layer thickness at baseline (Day1). Muscle ultrasound resulted as a feasible method for assessing muscle changes during acute phase of critical illness. Correlation between muscle layer thickness and APACHEscore at ICU admission could represent a role of muscle mass in the prognostic response to critical illness.

Mitochondrial dysfunction in critical illness during acute metabolic stress and convalescence: consequences for nutrition therapy.

Mitochondrial dysfunction is associated with increased morbidity and mortality during and after critical illness. The concept of adaptive mitochondrial metabolic-bio-energetic downregulation rather than bio-energetic failure during the acute phase of critical illness has gained traction. As mitochondria are not able to utilize substrate during adaptive hibernation and aggressive feeding induces further harm, this condition has consequences for nutrition therapy. Meeting resting energy expenditure in early critical illness is associated with enhanced oxidative stress and attenuation of autophagy, as is hyperglycemia. The negative effect of early high protein administration remains unclear, whereas fat appears bio-energetically inert. Although antioxidant micronutrients are essential to mitochondrial function, high-dosage studies of single vitamins (C and D) failed to show benefit. Convalescence probably requires increased micronutrient and macronutrient administration to aid anabolism and restore mitochondrial function, although robust data on requirements and actual intake are lacking. Optimal nutrition therapy in the early phase of critical illness should avoid overfeeding and preserve (adaptive) mitochondrial function. Micronutrient supplementation probably requires a strategic cocktail instead of a high dosage of a single nutrient. Focus on identification of distinct metabolic phases to adapt nutrition during and after critical illness is essential.

Micronutrient status during paediatric critical illness: A scoping review.

SummaryBackgroundNo evidence based recommendations for micronutrient requirements during paediatric critical illness are available, other than those arising from recommended nutrient intakes (RNI) for healthy children and expert opinion.ObjectivesThe objective of this review is to examine the available evidence from micronutrient status in critically ill children considering studies which describe 1) micronutrient levels, 2) associations between micronutrient levels and clinical outcome, and 3) impact on clinical outcome with micronutrient supplementation during PICU admission.DesignScoping review.Eligibility criteriaAny study which used a qualitative and quantitative design considering causes and consequences of micronutrient levels or micronutrient supplementation during paediatric critical illness.Sources of evidenceNICE Healthcare Databases Advanced Search website (https://hdas.nice.org.uk/) was used as a tool for multiple searches, with a content analysis and charting of data extracted.Results711 records were identified, 35 were included in the review. Studies evaluated serum micronutrient status was determined on admission day in majority of patients. A content analysis identified (n = 49) initial codes, (n = 14) sub-categories and (n = 5) overarching themes during critical illness, which were identified as: i) low levels of micronutrients, ii) causes of aberrant micronutrient levels, iii) associations between micronutrients levels and outcome, iv) supplementation of micronutrients.ConclusionDuring critical illness, micronutrients should be provided in sufficient amounts to meet reference nutrient intakes for age. Although, there is insufficient data to recommend routine supplementations of micronutrients at higher doses during critical illness, the ‘absence of evidence should not imply evidence of absence’, and well designed prospective studies are urgently needed to elucidate paediatric micronutrient requirements during critical illness. The absence of reliable biomarkers make it challenging to determine whether low serum levels are reflective of a true deficiency or as a result redistribution, particularly during the acute phase of critical illness. As more children continue to survive a PICU admission, particularly those with complex diseases micronutrient supplementation research should also be inclusive of the recovery phase following critical illness.

How 217 Pediatric Intensivists Manage Anemia at PICU Discharge: Online Responses to an International Survey.

To describe the management of anemia at PICU discharge by pediatric intensivists. Self-administered, online, scenario-based survey. PICUs in Australia/New Zealand, Europe, and North America. Pediatric intensivists. None. Respondents were asked to report their decisions regarding RBC transfusions, iron, and erythropoietin prescription to children ready to be discharged from PICU, who had been admitted for hemorrhagic shock, cardiac surgery, craniofacial surgery, and polytrauma. Clinical and biological variables were altered separately in order to assess their effect on the management of anemia. Two-hundred seventeen responses were analyzed. They reported that the mean (± SEM) transfusion threshold was a hemoglobin level of 6.9 ± 0.09 g/dL after hemorrhagic shock, 7.6 ± 0.10 g/dL after cardiac surgery, 7.0 ± 0.10 g/dL after craniofacial surgery, and 7.0 ± 0.10 g/dL after polytrauma (p < 0.001). The most important increase in transfusion threshold was observed in the presence of a cyanotic heart disease (mean increase ranging from 1.80 to 2.30 g/dL when compared with baseline scenario) or left ventricular dysfunction (mean increase, 1.41-2.15 g/dL). One third of respondents stated that they would not prescribe iron at PICU discharge, regardless of the hemoglobin level or the baseline scenario. Most respondents (69.4-75.0%, depending on the scenario) did not prescribe erythropoietin. Pediatric intensivists state that they use restrictive transfusion strategies at PICU discharge similar to those they use during the acute phase of critical illness. Supplemental iron is less frequently prescribed than RBCs, and prescription of erythropoietin is uncommon. Optimal management of post-PICU anemia is currently unknown. Further studies are required to highlight the consequences of this anemia and to determine appropriate management.

Is slower advancement of enteral feeding superior to aggressive full feeding regimens in the early phase of critical illness.

An excessive caloric intake during the acute phase of critical illness is associated with adverse effects, presumably related to overfeeding, inhibition of autophagy and refeeding syndrome. The purpose of this review is to summarize recently published clinical evidence in this area. Several observational studies, a few interventional trials, and systematic reviews/metaanalyses were published in 2017-2019. Most observational studies reported an association between caloric intakes below 70% of energy expenditure and a better vital outcome. In interventional trials, or systematic reviews, neither a benefit nor a harm was related to increases or decreases in caloric intake. Gastrointestinal dysfunction can be worsened by forced enteral feeding, whereas the absorption of nutrients can be impaired. Owing to the risks of the delivery of an excessive caloric intake, a strategy of permissive underfeeding implying a caloric intake matching a maximum of 70% of energy expenditure provides the best risk-to-benefit ratio during the acute phase of critical illness.

Management of HIV-infected patients in the intensive care unit.

The widespread use of combination antiretroviral therapies (cART) has converted the prognosis of HIV infection from a rapidly progressive and ultimately fatal disease to a chronic condition with limited impact on life expectancy. Yet, HIV-infected patients remain at high risk for critical illness due to the occurrence of severe opportunistic infections in those with advanced immunosuppression (i.e., inaugural admissions or limited access to cART), a pronounced susceptibility to bacterial sepsis and tuberculosis at every stage of HIV infection, and a rising prevalence of underlying comorbidities such as chronic obstructive pulmonary diseases, atherosclerosis or non-AIDS-defining neoplasms in cART-treated patients aging with controlled viral replication. Several patterns of intensive care have markedly evolved in this patient population over the late cART era, including a steady decline in AIDS-related admissions, an opposite trend in admissions for exacerbated comorbidities, the emergence of additional drivers of immunosuppression (e.g., anti-neoplastic chemotherapy or solid organ transplantation), the management of cART in the acute phase of critical illness, and a dramatic progress in short-term survival that mainly results from general advances in intensive care practices. Besides, there is a lack of data regarding other features of ICU and post-ICU care in these patients, especially on the impact of sociological factors on clinical presentation and prognosis, the optimal timing of cART introduction in AIDS-related admissions, determinants of end-of-life decisions, long-term survival, and functional outcomes. In this narrative review, we sought to depict the current evidence regarding the management of HIV-infected patients admitted to the intensive care unit.

The epidemiology of overfeeding in mechanically ventilated intensive care patients

Nutrition research in the Intensive Care Unit (ICU) typically focusses on the epidemiology of underfeeding, particularly early in the ICU admission. Once the acute phase of critical illness has resolved, patients may be at risk of overfeeding. We assessed for the frequency and consequences of potential overfeeding in ICU patients mechanically ventilated (MV) for at least 10 days. Retrospective analysis of 105MV patients including caloric input, estimated caloric requirements using the Schofield equation, and association between caloric input and several pre-defined clinical outcomes. To increase likelihood of detecting overfeeding, we conducted a post-hoc sensitivity analysis for sub-groups of patients who received on average<25kcal/kg/day (N=55) and >30kcal/kg/day (N=17) between day 7-10 and performed repeat ANOVA. There were no differences in the pre-defined outcomes for those given over, and below 25kcal/kg/day. On each study day, approximately 25% of patients received >30kcal/kg/day. Higher caloric delivery was statistically associated with increased minute ventilation on each study day (Spearman Rho approx 0.27;p≤0.007) and also in sub-group analysis (p<0.001). Higher caloric delivery was also associated with more frequent diarrhoea (p=0.02) and greater insulin requirement. However, these differences did not translate into increased duration of mechanical ventilation, length of stay, or increased mortality. Higher caloric intake was less strongly associated with serum urea and creatinine, but not associated with agitation, abnormal liver function tests, fever, or antibiotic prescription. Delivery of more than 25kcal/kg/day was not associated with adverse outcomes. On post-hoc analysis, delivery of more than 30kcal/kg/day was associated with increased minute ventilation, diarrhoea and insulin requirements but no differences in length of ventilation or in-hospital mortality.

Metabolic aspects of muscle wasting during critical illness.

Purpose of reviewSkeletal muscle wasting during critical illness is the result of disturbed metabolism. No proven effective interventions targeting skeletal muscle mass and function during critical illness currently exist. This review summarizes recent advances regarding the complexity of metabolic factors involved and the challenge of establishing the clinical effects of metabolic interventions targeting the muscle.Recent findingsAlthough the catabolic state is limited to the acute phase of critical illness, its subsequent impact on muscle mass and function persists long after ICU discharge. Immobilization, inflammation and disturbed muscle energy and nutrient metabolism are key drivers of muscle protein loss. Current research focuses on the effects of enhanced protein provision, specific substrate delivery and physical exercise. Whilst some interventions have been successful at improving muscle mass, these effects do not always carry over into muscle function or strength.SummaryIncreased understanding of metabolic derangements during critical illness provides new potential targets for treatment. The potential of dietary protein to attenuate the muscle protein catabolic state has yet to be established in clinical trials. Basic research should focus on ways to further improve the anabolic potential of nutrition by unravelling mechanisms that regulate anabolic and catabolic pathways and energy metabolism.

Anterior pituitary function in critical illness.

Critical illness is hallmarked by major changes in all hypothalamic–pituitary–peripheral hormonal axes. Extensive animal and human studies have identified a biphasic pattern in circulating pituitary and peripheral hormone levels throughout critical illness by analogy with the fasting state. In the acute phase of critical illness, following a deleterious event, rapid neuroendocrine changes try to direct the human body toward a catabolic state to ensure provision of elementary energy sources, whereas costly anabolic processes are postponed. Thanks to new technologies and improvements in critical care, the majority of patients survive the acute insult and recover within a week. However, an important part of patients admitted to the ICU fail to recover sufficiently, and a prolonged phase of critical illness sets in. This prolonged phase of critical illness is characterized by a uniform suppression of the hypothalamic–pituitary–peripheral hormonal axes. Whereas the alterations in hormonal levels during the first hours and days after the onset of critical illness are evolutionary selected and are likely beneficial for survival, endocrine changes in prolonged critically ill patients could be harmful and may hamper recovery. Most studies investigating the substitution of peripheral hormones or strategies to overcome resistance to anabolic stimuli failed to show benefit for morbidity and mortality. Research on treatment with selected and combined hypothalamic hormones has shown promising results. Well-controlled RCTs to corroborate these findings are needed.

Gut rest strategy and trophic feeding in the acute phase of critical illness with acute gastrointestinal injury.

Critically ill patients frequently suffer from gastrointestinal dysfunction as the intestine is a vulnerable organ. In critically ill patients who require nutritional support, the current guidelines recommend the use of enteral nutrition within 24-48 h and advancing towards optimal nutritional goals over the next 48-72 h; however, this may be contraindicated in patients with acute gastrointestinal injury because overuse of the gut in the acute phase of critical illness may have an adverse effect on the prognosis. We propose that trophic feeding after 72 h, as a partial gut rest strategy, should be provided to critically ill patients during the acute phase of illness as an organ-protective strategy, especially for those with acute gastrointestinal injury.

Abstracts of the 11th International Conference on Cachexia, Sarcopenia and Muscle Wasting, Maastricht, The Netherlands, 7–9 December 2018 (Part 2)

Abstracts of the 11^th International Conference on Cachexia, Sarcopenia and Muscle Wasting, Maastricht, The Netherlands, 7–9 December 2018 (Part 2)

Sleep and Intensive Care Unit-Acquired Weakness in Critically Ill Older Adults.

Older adults in the intensive care unit (ICU) often experience sleep disturbances, which may stem from life-threatening illness, the ICU environment, medications/sedation, or psychological stress. Two complementary endocrinological responses occur as a result of compromised sleep and consequently could exacerbate ICU-acquired weakness: a decrease in anabolic hormones leading to decreased protein synthesis and an increase in catabolic hormones leading to increased protein degradation. Age-associated decreases in anabolic hormones, such as insulin-like growth factor 1, testosterone, and growth hormone, may inhibit protein synthesis. Likewise, age-associated increases in insulin resistance, glucocorticoids, and myostatin can stimulate muscle atrophy and further reduce protein synthesis. Thus, perhaps, sleep promotion in the ICU may attenuate muscle atrophy among critically ill older adults who are at risk for ICU-acquired weakness and subsequent functional decline. The aim of this study was to discuss the hypothesized theoretical underpinnings of the relationship between sleep disturbances and ICU-acquired weakness among critically ill older adults. A search of research literature published from 1970 to 2018 and indexed in MEDLINE, Embase, CINAHL, and Ovid was undertaken, and relevant sources were selected to build an informed discussion. Nurses must be mindful of secondary sleep disturbances that occur throughout the acute phase of critical illness and their probable links to ICU-acquired weakness. Targeted interventions to promote functional outcomes in elderly patients should consider this relationship. Improved sleep may have the potential to decrease the severity of muscle atrophy and ICU-acquired weakness. Future research must explore this hypothesis and the underlying mechanisms of the association between sleep disturbances and ICU-acquired weakness in critically ill older adults.

Effectiveness of functional outcomes among critically-ill patients receiving early mobilization and early nutrition support

Rationale: Skeletal muscle wasting is observed in the acute phase of critical illness; however, functional outcomes have not been proven clearly. Early mobilization of critically-ill patients receiving early nutrition support may improve functional outcome. This study aimed to assess the effect of early mobilization in critically-ill patients receiving early nutrition support.

Trophic or full nutritional support?

Full nutritional support during the acute phase of critical illness has traditionally been recommended to reduce catabolism and prevent malnutrition. Approaches to achieve full nutrition include early initiation of nutritional support, targeting full nutritional requirement as soon as possible and initiation of supplemental parenteral nutrition when enteral nutrition does not reach the target. Existing evidence supports early enteral nutrition over delayed enteral nutrition or early parenteral nutrition. Recent randomized controlled trials have demonstrated that permissive underfeeding or trophic feeding is associated with similar outcomes compared with full feeding in the acute phase of critical illness. In patients with refeeding syndrome, patients with high nutritional risk and patients with shock, early enteral nutrition targeting full nutritional targets may be associated with worse outcomes compared with less aggressive enteral nutrition strategy. A two-phase approach for nutritional support may more appropriately account for the physiologic changes during critical illness than one-phase approach. Further evidence is awaited for the optimal protein amount during critical illness and for feeding patients at high nutritional risk or with acute gastrointestinal injury.

Plasma non-esterified fatty acids (NEFA) concentrations may decrease with a glucose based parenteral nutrition regime

Aim: Lipolysis is accelerated during the acute phase of critical illness. The mechanisms related to total parenteral nutrition (TPN) remain elusive and we therefore measured NEFA concentrations in a random set of patients from a larger ongoing clinical trial comparing metabolic changes in critically ill patients randomized to receive TPN containing nonprotein calories entirely from glucose or in combination with a fat emulsion (SMOFlipid).

Autophagy and Its Implications Against Early Full Nutrition Support in Critical Illness

The timing, dose, and route of early nutrition support in critically ill patients have been highly controversial for years. Despite the association of a caloric deficit with adverse outcome, several recent large, randomized, controlled trials have demonstrated a prolongation of organ failure and increased muscle weakness with increasing doses of nutrition in the acute phase of critical illness. A potential explanation for the negative impact of early, full feeding on outcome is feeding-induced suppression of autophagy, a cellular repair process that is necessary to clear intracellular damage. Whether nutrition management in critically ill patients should be guided by its effects on autophagy is a topic of debate. Currently, however, autophagy cannot be monitored in clinical practice. Moreover, clinical management should be guided by high-quality randomized controlled trials, which currently do not support the use of early full nutrition support.