Convalescent Plasma for Covid-19-Induced ARDS in Mechanically Ventilated Patients.

BACKGROUND: Passive immunization with plasma collected from convalescent patients has been regularly used to treat coronavirus disease 2019 (Covid-19). Minimal data are available regarding the use of convalescent plasma in patients with Covid-19-induced acute respiratory distress syndrome (ARDS). METHODS: In this open-label trial, we randomly assigned adult patients with Covid-19-induced ARDS who had been receiving invasive mechanical ventilation for less than 5 days in a 1:1 ratio to receive either convalescent plasma with a neutralizing antibody titer of at least 1:320 or standard care alone. Randomization was stratified according to the time from tracheal intubation to inclusion. The primary outcome was death by day 28. RESULTS: A total of 475 patients underwent randomization from September 2020 through March 2022. Overall, 237 patients were assigned to receive convalescent plasma and 238 to receive standard care. Owing to a shortage of convalescent plasma, a neutralizing antibody titer of 1:160 was administered to 17.7% of the patients in the convalescent-plasma group. Glucocorticoids were administered to 466 patients (98.1%). At day 28, mortality was 35.4% in the convalescent-plasma group and 45.0% in the standard-care group (P = 0.03). In a prespecified analysis, this effect was observed mainly in patients who underwent randomization 48 hours or less after the initiation of invasive mechanical ventilation. Serious adverse events did not differ substantially between the two groups. CONCLUSIONS: The administration of plasma collected from convalescent donors with a neutralizing antibody titer of at least 1:160 to patients with Covid-19-induced ARDS within 5 days after the initiation of invasive mechanical ventilation significantly reduced mortality at day 28. This effect was mainly observed in patients who underwent randomization 48 hours or less after ventilation initiation. (Funded by the Belgian Health Care Knowledge Center; ClinicalTrials.gov number, NCT04558476.).

Investigation of parenteral nutrition-induced hepatotoxicity using human liver spheroid co-cultures.

Parenteral nutrition (PN) is typically administered to individuals with gastrointestinal dysfunction, a contraindication for enteral feeding, and a need for nutritional therapy. When PN is the only energy source in patients, it is defined as total parenteral nutrition (TPN). TPN is a life-saving approach for different patient populations, both in infants and adults. However, despite numerous benefits, TPN can cause adverse effects, including metabolic disorders and liver injury. TPN-associated liver injury, known as intestinal failure-associated liver disease (IFALD), represents a significant problem affecting up to 90% of individuals receiving TPN. IFALD pathogenesis is complex, depending on the TPN components as well as on the patient's medical conditions. Despite numerous animal studies and clinical observations, the molecular mechanisms driving IFALD remain largely unknown. The present study was set up to elucidate the mechanisms underlying IFALD. For this purpose, human liver spheroid co-cultures were treated with a TPN mixture, followed by RNA sequencing analysis. Subsequently, following exposure to TPN and its single nutritional components, several key events of liver injury, including mitochondrial dysfunction, endoplasmic reticulum stress, oxidative stress, apoptosis, and lipid accumulation (steatosis), were studied using various techniques. It was found that prolonged exposure to TPN substantially changes the transcriptome profile of liver spheroids and affects multiple metabolic and signaling pathways contributing to liver injury. Moreover, TPN and its main components, especially lipid emulsion, induce changes in all key events measured and trigger steatosis.

Post-ICU nutrition: the neglected side of metabolic support.

PURPOSE OF THIS REVIEW: This review will focus on the neglected side of metabolic support in ICU survivors: nutritional therapy after critical illness. Knowledge of the evolution of the metabolism of patients that survived critical illness will be bundled, and current practices will be investigated. We will discuss some studies conducted to determine resting energy expenditure in ICU survivors and which identified barriers that cause interruptions in the feeding process based on published data between January 2022 and April 2023. RECENT FINDINGS: Resting energy expenditure can be measured using indirect calorimetry, as predictive equations have proven to fail in their attempt to have good correlations with measured values. No guidelines or recommendations are available on post-ICU follow-up, including screening, assessment, dosing, timing, and monitoring of (artificial) nutrition. A limited number of publications shared treatment adequacy between 64-82% for energy (calories) and 72-83% for protein intake in a post-ICU setting. Loss of appetite, depression, and oropharyngeal dysphagia are the most prominent physiological barriers responsible for decreased feeding adequacy. SUMMARY: Patients may be in a catabolic state during and after ICU discharge, with several factors impacting metabolism. Therefore, large prospective trials are needed to determine the physiological state of ICU survivors, determine nutritional requirements, and develop nutritional care protocols. Many barriers causing decreased feeding adequacy have already been identified, but solutions are scarce. This review depicts a variable metabolic rate among ICU survivors and a significant variation in feeding adequacy in-between world regions, institutions, and patient sub-phenotypes.

Personalized nutrition therapy in critical care: 10 expert recommendations.

Personalization of ICU nutrition is essential to future of critical care. Recommendations from American/European guidelines and practice suggestions incorporating recent literature are presented. Low-dose enteral nutrition (EN) or parenteral nutrition (PN) can be started within 48 h of admission. While EN is preferred route of delivery, new data highlight PN can be given safely without increased risk; thus, when early EN is not feasible, provision of isocaloric PN is effective and results in similar outcomes. Indirect calorimetry (IC) measurement of energy expenditure (EE) is recommended by both European/American guidelines after stabilization post-ICU admission. Below-measured EE (~ 70%) targets should be used during early phase and increased to match EE later in stay. Low-dose protein delivery can be used early (~ D1-2) (< 0.8 g/kg/d) and progressed to ≥ 1.2 g/kg/d as patients stabilize, with consideration of avoiding higher protein in unstable patients and in acute kidney injury not on CRRT. Intermittent-feeding schedules hold promise for further research. Clinicians must be aware of delivered energy/protein and what percentage of targets delivered nutrition represents. Computerized nutrition monitoring systems/platforms have become widely available. In patients at risk of micronutrient/vitamin losses (i.e., CRRT), evaluation of micronutrient levels should be considered post-ICU days 5-7 with repletion of deficiencies where indicated. In future, we hope use of muscle monitors such as ultrasound, CT scan, and/or BIA will be utilized to assess nutrition risk and monitor response to nutrition. Use of specialized anabolic nutrients such as HMB, creatine, and leucine to improve strength/muscle mass is promising in other populations and deserves future study. In post-ICU setting, continued use of IC measurement and other muscle measures should be considered to guide nutrition. Research on using rehabilitation interventions such as cardiopulmonary exercise testing (CPET) to guide post-ICU exercise/rehabilitation prescription and using anabolic agents such as testosterone/oxandrolone to promote post-ICU recovery is needed.

Indirect Calorimetry in Spontaneously Breathing, Mechanically Ventilated and Extracorporeally Oxygenated Patients: An Engineering Review.

Indirect calorimetry (IC) is considered the gold standard for measuring resting energy expenditure (REE). This review presents an overview of the different techniques to assess REE with special regard to the use of IC in critically ill patients on extracorporeal membrane oxygenation (ECMO), as well as to the sensors used in commercially available indirect calorimeters. The theoretical and technical aspects of IC in spontaneously breathing subjects and critically ill patients on mechanical ventilation and/or ECMO are covered and a critical review and comparison of the different techniques and sensors is provided. This review also aims to accurately present the physical quantities and mathematical concepts regarding IC to reduce errors and promote consistency in further research. By studying IC on ECMO from an engineering point of view rather than a medical point of view, new problem definitions come into play to further advance these techniques.

Effect of extracorporeal carbon dioxide removal on respiratory quotient measured by indirect calorimetry: Unravelling the mystery.

NEW FINDINGS: What is the main observation in this case? Several studies have reported progressive hypoxaemia once extracorporeal carbon dioxide removal is started in patients with hypercapnic respiratory failure, possibly attributable to an altered respiratory quotient. What insights does it reveal? In this quality control report, we show that the respiratory quotient exhibits only minimal alteration when extracorporeal carbon dioxide removal is started and assume that the progressive hypoxaemia is attributable to an increase in intrapulmonary shunt. ABSTRACT: The use of extracorporeal carbon dioxide removal (ECCO2 R) has been proposed in patients with acute respiratory distress syndrome to achieve lung-protective ventilation and in patients with selective hypercapnic respiratory failure. However, several studies have reported progressive hypoxaemia, as expressed by a need to increase the inspired oxygen fraction (Fi O2 ) to maintain adequate oxygenation or by a decrease in the ratio of arterial oxygen tension (Pa O2 ) to Fi O2 once ECCO2 R is started. We present the case of a patient who was admitted to the intensive care unit for a coronavirus disease 2019 pneumonia and who was intubated because of hypercapnic respiratory insufficiency. Extracorporeal carbon dioxide removal was started, and the patient subsequently developed progressive hypoxaemia. To test whether the hypoxaemia was attributable to the ECCO2 R, blood samples were taken in different settings: (1) 'no ECCO2 R', blood flow 150 ml/min with a ECCO2 R gas flow of 0 L/min; and (2) 'with ECCO2 R', blood flow 400 ml/min with gas flow 12 L/min. We measured Pa O2 , alveolar oxygen tension, Pa O2 /Fi O2 , alveolar-arterial oxygen tension difference, arterial carbon dioxide tension and the respiratory quotient (RQ) by indirect calorimetry in each setting. The RQ was 0.60 without ECCO2 R and 0.57 with ECCO2 R. The alveolar oxygen tension was 220.4 mmHg without ECCO2 R and increased to 240.3 mmHg with ECCO2 R, whereas Pa O2 /Fi O2 decreased from 177 to 171. Our study showed only a minimal change in RQ when ECCO2 R was started. We were the first to measure the RQ directly, before and after the initiation of ECCO2 R, in a patient with hypercapnic respiratory failure.

Post-Traumatic Stress Disorder after COVID-19 Intensive Care admission: Characteristics and Perspectives.

An increase of psychopathology such as post-traumatic stress disorder (PTSD) is described in patients affected with COVID-19 that stayed at an intensive care unit (ICU). However, data on follow-up and on impact of contextual factors are limited. In a single-center, observational study, PTSD symptomatology was prevalent among 38% of participants (n=8), persisting in clinical PTSD in 2 participants after one year. In patients with initial PTSD symptoms, scores on depression, anxiety and insomnia scales were significantly higher. A higher mental burden due to avoidance of contact and a reduced quality of life was also retained in patients with PTSD symptoms.

Indirect calorimetry in critical illness: a new standard of care?

PURPOSE OF REVIEW: Review recent literature on the role of indirect calorimetry in critical care nutrition management. RECENT FINDINGS: Critical illness demands objective, targeted nutritional therapy to prevent adverse effects of underfeeding/over feeding. Thus, all recent societal guidelines recommend indirect calorimetry use to determine energy needs. Very recently, indirect calorimetry technology has finally evolved to allow for accurate, simple, and routine utilization in a wider range of ICU patients. Recent data continues to confirm poor correlation between measured and equation-predicted energy expenditure emphasizing need for indirect calorimetry to be standard of care. This may be particularly true in COVID-19, where significant progressive hypermetabolism and variability in energy expenditure has been shown. Metabolic physiology can change frequently during ICU stay in response to changes in clinical condition or care. Thus, repeated longitudinal indirect calorimetry measures are needed throughout ICU stay to optimize care, with initial data showing improved clinical outcomes when indirect calorimetry targets are utilized. SUMMARY: Personalized ICU care demands objective data to guide therapy. This includes use of indirect calorimetry to determine energy expenditure and guide ICU nutrition therapy. Long-awaited new innovations in indirect calorimetry technology should finally lead to indirect calorimetry to becoming a fundamental component of modern ICU standard of care and clinical research moving forward.

Nutrients and micronutrients at risk during renal replacement therapy: a scoping review.

PURPOSE OF REVIEW: Malnutrition is frequent in patients with acute kidney injury. Nutrient clearance during renal replacement therapy (RRT) potentially contributes to this complication. Although losses of amino acid, trace elements and vitamins have been described, there is no clear guidance regarding the role of micronutrient supplementation. RECENT FINDINGS: A scoping review was conducted with the aim to review the existing literature on micronutrients status during RRT: 35 publications including data on effluent losses and blood concentrations were considered relevant and analysed. For completeness, we also included data on amino acids. Among trace elements, negative balances have been shown for copper and selenium: low blood levels seem to indicate potential deficiency. Smaller size water soluble vitamins were found in the effluent, but not larger size liposoluble vitamins. Low blood values were frequently reported for thiamine, folate and vitamin C, as well as for carnitine. All amino acids were detectable in effluent fluid. Duration of RRT was associated with decreasing blood values. SUMMARY: Losses of several micronutrients and amino acids associated with low blood levels represent a real risk of deficiency for vitamins B1 and C, copper and selenium: they should be monitored in prolonged RRT. Further Research is urgently required as the data are insufficient to generate strong conclusions and prescription recommendations for clinical practice.

An endotracheal tube providing "pressurized sealing" prevents fluid leakage in mechanically ventilated critically ill patients: a pilot study.

Microaspiration of bacteriologically contaminated oropharyngeal secretions alongside the cuff of an endotracheal tube (ETT) is a key mechanism for development of ventilator-associated pneumonia. We have constructed a prototype double-cuffed ETT equipped with a supplemental port in-between the cuffs through which continuous positive airway pressure (CPAP) is delivered. Pressure in the intercuff space propels secretions upwards and produces 100% tracheal sealing in an in vitro model. We conducted a 24 h study to investigate the sealing effect of this ETT in 12 critically ill mechanically ventilated patients. Methylene blue, instilled through a bronchoscope on top of the proximal cuff, was used as leakage tracer. Fiberoptic visualisation of the trachea was performed 1 h and 24 h thereafter. Leakage was confirmed if blue dye was detected on the tracheal mucosa beyond the tip of the ETT. In no patient, dye passed by the cuffs during the study period. Presence of the ETT did not interfere with ventilator settings, patient mobilization, physiotherapy, and technical acts. Overall, pressures in the intercuff space remained between 10 and 15 cmH2O. Excessive pressure swings were swiftly corrected by the CPAP system. A double-cuffed ETT, offering "pressurized sealing" of the trachea, safely and effectively prevented leakage during 24 h mechanical ventilation.

How to deal with severe acute pancreatitis in the critically ill.

PURPOSE OF REVIEW: To review recent literature on the management of patients with severe acute pancreatitis (SAP) admitted to an ICU. RECENT FINDINGS: SAP is a devastating disease associated with a high morbidity and mortality. Recent evidence advocates adequate risk assessment and severity prediction (including intra-abdominal pressure monitoring), tailored fluid administration favoring balanced crystalloids, withholding prophylactic antibiotic therapy, and early detection and treatment of extra-pancreatic and fungal infections. Urgent (within 24-48 h after diagnosis) endoscopic retrograde cholangiopancreatography is indicated when persistent biliary obstruction or cholangitis are present. Corticosteroid therapy (mainly dexamethasone) can reduce the need for surgical interventions, length of hospital stay, and mortality. Peritoneal lavage may significantly lower morbidity and mortality. Hemofiltration may offer substantial benefit but more studies are needed to prove its efficacy. Enteral feeding using a polymeric formula and provided early through a nasogastric tube is recommended but has no survival benefit compared with parenteral nutrition. Probiotics could be beneficial, however no clear recommendations can be made. SUMMARY: Management of SAP is multimodal with emphasis on monitoring, adequate fluid resuscitation, avoiding prophylactic use of antibiotics, cause-directed procedures or treatment, and organ support. There is a role for early enteral nutrition including probiotics.

Nutrition therapy and critical illness: practical guidance for the ICU, post-ICU, and long-term convalescence phases.

BACKGROUND: Although mortality due to critical illness has fallen over decades, the number of patients with long-term functional disabilities has increased, leading to impaired quality of life and significant healthcare costs. As an essential part of the multimodal interventions available to improve outcome of critical illness, optimal nutrition therapy should be provided during critical illness, after ICU discharge, and following hospital discharge. METHODS: This narrative review summarizes the latest scientific insights and guidelines on ICU nutrition delivery. Practical guidance is given to provide optimal nutrition therapy during the three phases of the patient journey. RESULTS: Based on recent literature and guidelines, gradual progression to caloric and protein targets during the initial phase of ICU stay is recommended. After this phase, full caloric dose can be provided, preferably based on indirect calorimetry. Phosphate should be monitored to detect refeeding hypophosphatemia, and when occurring, caloric restriction should be instituted. For proteins, at least 1.3 g of proteins/kg/day should be targeted after the initial phase. During the chronic ICU phase, and after ICU discharge, higher protein/caloric targets should be provided preferably combined with exercise. After ICU discharge, achieving protein targets is more difficult than reaching caloric goals, in particular after removal of the feeding tube. After hospital discharge, probably very high-dose protein and calorie feeding for prolonged duration is necessary to optimize the outcome. High-protein oral nutrition supplements are likely essential in this period. Several pharmacological options are available to combine with nutrition therapy to enhance the anabolic response and stimulate muscle protein synthesis. CONCLUSIONS: During and after ICU care, optimal nutrition therapy is essential to improve the long-term outcome to reduce the likelihood of the patient to becoming a "victim" of critical illness. Frequently, nutrition targets are not achieved in any phase of recovery. Personalized nutrition therapy, while respecting different targets during the phases of the patient journey after critical illness, should be prescribed and monitored.

Metabolic support in the critically ill: a consensus of 19.

Metabolic alterations in the critically ill have been studied for more than a century, but the heterogeneity of the critically ill patient population, the varying duration and severity of the acute phase of illness, and the many confounding factors have hindered progress in the field. These factors may explain why management of metabolic alterations and related conditions in critically ill patients has for many years been guided by recommendations based essentially on expert opinion. Over the last decade, a number of randomized controlled trials have been conducted, providing us with important population-level evidence that refutes several longstanding paradigms. However, between-patient variation means there is still substantial uncertainty when translating population-level evidence to individuals. A cornerstone of metabolic care is nutrition, for which there is a multifold of published guidelines that agree on many issues but disagree on others. Using a series of nine questions, we provide a review of the latest data in this field and a background to promote efforts to address the need for international consistency in recommendations related to the metabolic care of the critically ill patient. Our purpose is not to replace existing guidelines, but to comment on differences and add perspective.

Energy expenditure of patients on ECMO: A prospective pilot study.

BACKGROUND: An optimal nutritional approach sustained by convenient monitoring of metabolic status and reliable assessment of energy expenditure (EE) may improve the outcome of critically ill patients on extracorporeal membrane oxygenation (ECMO). We previously demonstrated the feasibility of indirect calorimetry (IC)-the standard of care technique to determine caloric targets-in patients undergoing ECMO. This study aims to compare measured with calculated EE during ECMO treatment. We additionally provide median EE values for use in settings where IC is not available. METHODS: IC was performed in seven stable ECMO patients. Gas exchange was analyzed at the ventilator, and ECMO side and values were introduced in a modified Weir formula to calculate resting EE. Results were compared with EE calculated with the Harris-Benedict equation and with the 25 kcal/kg/day ESPEN recommendation. RESULTS: Total median oxygen consumption rate was 196 (Q1-Q3 158-331) mL/min, and total median carbon dioxide production was 150 (Q1-Q3 104-203) mL/min. Clinically relevant differences between calculated and measured EE were observed in all patients. The median EE was 1334 (Q1-Q3 1134-2119) kcal/24 hours or 18 (Q1-Q3 15-27) kcal/kg/day. CONCLUSION: Compared with measured EE, calculation of EE both over- and underestimated caloric needs during ECMO treatment. Despite a median EE of 21 kcal/kg/day, large variability in metabolic rate was found and demands further investigation.

Correction to: CO2 and O2 removal during continuous veno-venous hemofiltration: a pilot study.

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CO2 and O2 removal during continuous veno-venous hemofiltration: a pilot study.

BACKGROUND: Carbon dioxide (CO2) accumulation is a challenging issue in critically ill patients. CO2 can be eliminated by renal replacement therapy but studies are scarce and clinical relevance is unknown. We prospectively studied CO2 and O2 behavior at different sample points of continuous veno-venous hemofiltration (CVVH) and build a model to calculate CO2 removal bedside. METHODS: In 10 patients receiving standard CVVH under citrate anticoagulation, blood gas analysis was performed at different sample points within the CVVH circuit. Citrate was then replaced by NaCl 0.9% and sampling was repeated. Total CO2 (tCO2), CO2 flow (V̇CO2) and O2 flow (V̇O2) were compared between different sample points. The effect of citrate on transmembrane tCO2 was evaluated. Wilcoxon matched-pairs signed rank test was performed to evaluate significance of difference between 2 data sets. Friedman test was used when more data sets were compared. RESULTS: V̇CO2 in the effluent (26.0 ml/min) correlated significantly with transmembrane V̇CO2 (24.2 ml/min). This represents 14% of the average expired V̇CO2 in ventilated patients. Only 1.3 ml/min CO2 was removed in the de-aeration chamber, suggesting that CO2 was almost entirely cleared across the membrane filter. tCO2 values in effluent, before, and after the filter were not statistically different. Transmembrane tCO2 under citrate or NaCl 0.9% predilution also did not differ significantly. No changes in V̇O2 were observed throughout the CVVH circuit. Based on recorded data, formulas were constructed that allow bedside evaluation of CVVH-attributable CO2 removal. CONCLUSION: A relevant amount of CO2 is removed by CVVH and can be quantified by one simple blood gas analysis within the circuit. Future studies should assess the clinical impact of this observation. TRIAL REGISTRATION: The trial was registered at https://clinicaltrials.gov with trial registration number NCT03314363 on October 192,017.

Does the use of indirect calorimetry change outcome in the ICU? Yes it does.

PURPOSE OF REVIEW: To review the recent findings on metabolic monitoring and possible beneficial effects of an adequate nutrition therapy, based on indirect calorimetry as the golden standard to predict energy expenditure. RECENT FINDINGS: in the last decades, major steps are taken in the field of metabolism and nutrition, evolving from nutrition as a baseline support to a therapeutic intervention. The aspect of energy expenditure is of cardinal importance, and technical possibilities have impressively improved: from the first 'calorimetre' in 1789 to the new generation, clinical applicable indirect calorimeters and the high accuracy and easy use model reaching high technology readiness level [Oshima et al. (2017). Clin Nutr 36:651]. Several recent studies provide information on the technique of metabolic monitoring itself and the positive effects of implementation of the tool in a high-end nutritional care plan [Oshima et al. (2017). Clin Nutr 36:651]. The combination of correct energy provision and protein prescription has shown benefits, and mortality of ICU patients is related to the amount of energy provided [Zusman et al. (2016). Crit Care 20:367]. The use of a monitor per se will not change outcome. Optimal dosing of artificial nutrition can be achieved by the use of a parameter acquired by a measurement instead of by inaccurate equations. In the era of precision medicine, this approach has shown positive effects on outcome. Moreover, above all, the concept of metabolic monitoring of the critically ill is just an issue of common sense. SUMMARY: Metabolic monitoring by indirect calorimetry is achieving a level in which it can be implemented in critical care practice. Evidence is available to prove that by guiding your nutritional therapy by measured values, it will change outcome of critically ill patients.

Statins and the Kidney: Friend or Foe?

Statins essentially are cholesterol-lowering drugs that are extensively prescribed for primary and secondary prevention of cardiovascular disease. Compelling evidence suggests that the beneficial effects of statins may not only be due to controlling cholesterol levels but also due to a pleiotropic cholesterol-independent anti-inflammatory, antioxidant, endothelial-protective and plaque-stabilizing activity. Along this line, statins may also exert acute and long-term effects on renal function. We present a narrative literature review that summarizes arguments in favour or against the preventive and/or therapeutic use of statins in kidney-related diseases or complications. We also highlight the ongoing controversy regarding statin therapy in chronic and end-stage kidney disease.

Renal blood flow and acute kidney injury in septic shock: an arduous conflict that smolders intrarenally?

Sepsis-induced acute kidney injury (SAKI) is traditionally viewed as a process driven by a reduced blood flow and prone to benefit from vasopressive support. In ovine hyperdynamic septic shock, Lankadeva et al. report a significant and flow-independent intrarenal perfusion and oxygenation "mismatch" jeopardizing the renal medulla that was aggravated by norepinephrine. Medullary and urinary oxygenation changed in parallel, suggesting that urinary oxygenation may act as a biomarker to predict SAKI.