Societal costs of sepsis in the Netherlands.

BACKGROUND: Sepsis is a life-threatening syndrome characterized by acute loss of organ function due to infection. Sepsis survivors are at risk for long-term comorbidities, have a reduced Quality of Life (QoL), and are prone to increased long-term mortality. The societal impact of sepsis includes its disease burden and indirect economic costs. However, these societal costs of sepsis are not fully understood. This study assessed sepsis's disease-related and indirect economic costs in the Netherlands. METHODS: Sepsis prevalence, incidence, sepsis-related mortality, hospitalizations, life expectancy, QoL population norms, QoL reduction after sepsis, and healthcare use post-sepsis were obtained from previous literature and Statistics Netherlands. We used these data to estimate annual Quality-adjusted Life Years (QALYs), productivity loss, and increase in healthcare use post-sepsis. A sensitivity analysis was performed to analyze the burden and indirect economic costs of sepsis under alternative assumptions, resulting in a baseline, low, and high estimated burden. The results are presented as a baseline (low-high burden) estimate. RESULTS: The annual disease burden of sepsis is approximately 57,304 (24,398-96,244; low-high burden) QALYs. Of this, mortality accounts for 26,898 (23,166-31,577) QALYs, QoL decrease post-sepsis accounts for 30,406 (1232-64,667) QALYs. The indirect economic burden, attributed to lost productivity and increased healthcare expenditure, is estimated at €416.1 (147.1-610.7) million utilizing the friction cost approach and €3.1 (0.4-5.7) billion using the human capital method. Cumulatively, the combined disease and indirect economic burdens range from €3.8 billion (friction method) to €6.5 billion (human capital method) annually within the Netherlands. CONCLUSIONS: Sepsis and its complications pose a substantial disease and indirect economic burden to the Netherlands, with an indirect economic burden due to production loss that is potentially larger than the burden due to coronary heart disease or stroke. Our results emphasize the need for future studies to prevent sepsis, saving downstream costs and decreasing the economic burden.

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.

Intermittent feeding and circadian rhythm in critical illness.

PURPOSE OF REVIEW: Circadian rhythms, i.e., periodic oscillations in internal biological processes, modulate metabolic processes such as hormonal signalling, nutrient absorption, and xenobiotic detoxification. Meal timing is a strong entraining cue for peripheral clocks in various organs, and eating out of circadian phases can impair glucose, gastrointestinal, and muscle metabolism. Sleep/wake cycles and circadian rhythms are extremely disrupted during critical illness. Timing of nutritional support may help preserve circadian rhythms and improve post-Intensive Care Unit (ICU) recovery. This review summarises circadian disruptors during ICU admission and evaluates the potential benefits of intermittent feeding on metabolism and circadian rhythms. RECENT FINDINGS: Rhythmic expression of core clock genes becomes rapidly disturbed during critical illness and remains disturbed for weeks. Intermittent, bolus, and cyclic enteral feeding have been directly compared to routine continuous feeding, yet no benefits on glycaemic control, gastrointestinal tolerance, and muscle mass have been observed and impacts of circadian clocks remain untested. SUMMARY: Aligning timing of nutritional intake, physical activity, and/or medication with circadian rhythms are potential strategies to reset peripheral circadian rhythms and may enhance ICU recovery but is not proven beneficial yet. Therefore, selecting intermittent feeding over continuous feeding must be balanced against the pros and cons of clinical practice.

The 2021 Dutch Working Party on Antibiotic Policy (SWAB) guidelines for empirical antibacterial therapy of sepsis in adults.

BACKGROUND: The Dutch Working Party on Antibiotic Policy (SWAB) in collaboration with relevant professional societies, has updated their evidence-based guidelines on empiric antibacterial therapy of sepsis in adults. METHODS: Our multidisciplinary guideline committee generated ten population, intervention, comparison, and outcome (PICO) questions relevant for adult patients with sepsis. For each question, a literature search was performed to obtain the best available evidence and assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. The quality of evidence for clinically relevant outcomes was graded from high to very low. In structured consensus meetings, the committee formulated recommendations as strong or weak. When evidence could not be obtained, recommendations were provided based on expert opinion and experience (good practice statements). RESULTS: Fifty-five recommendations on the antibacterial therapy of sepsis were generated. Recommendations on empiric antibacterial therapy choices were differentiated for sepsis according to the source of infection, the potential causative pathogen and its resistance pattern. One important revision was the distinction between low, increased and high risk of infection with Enterobacterales resistant to third generation cephalosporins (3GRC-E) to guide the choice of empirical therapy. Other new topics included empirical antibacterial therapy in patients with a reported penicillin allergy and the role of pharmacokinetics and pharmacodynamics to guide dosing in sepsis. We also established recommendations on timing and duration of antibacterial treatment. CONCLUSIONS: Our multidisciplinary committee formulated evidence-based recommendations for the empiric antibacterial therapy of adults with sepsis in The Netherlands.

Obesity and critical care nutrition: current practice gaps and directions for future research.

BACKGROUND: This review has been developed following a panel discussion with an international group of experts in the care of patients with obesity in the critical care setting and focuses on current best practices in malnutrition screening and assessment, estimation of energy needs for patients with obesity, the risks and management of sarcopenic obesity, the value of tailored nutrition recommendations, and the emerging role of immunonutrition. Patients admitted to the intensive care unit (ICU) increasingly present with overweight and obesity that require individualized nutrition considerations due to underlying comorbidities, immunological factors such as inflammation, and changes in energy expenditure and other aspects of metabolism. While research continues to accumulate, important knowledge gaps persist in recognizing and managing the complex nutritional needs in ICU patients with obesity. Available malnutrition screening and assessment tools are limited in patients with obesity due to a lack of validation and heterogeneous factors impacting nutrition status in this population. Estimations of energy and protein demands are also complex in patients with obesity and may include estimations based upon ideal, actual, or adjusted body weight. Evidence is still sparse on the role of immunonutrition in patients with obesity, but the presence of inflammation that impacts immune function may suggest a role for these nutrients in hemodynamically stable ICU patients. Educational efforts are needed for all clinicians who care for complex cases of critically ill patients with obesity, with a focus on strategies for optimal nutrition and the consideration of issues such as weight stigma and bias impacting the delivery of care. CONCLUSIONS: Current nutritional strategies for these patients should be undertaken with a focus on individualized care that considers the whole person, including the possibility of preexisting comorbidities, altered metabolism, and chronic stigma, which may impact the provision of nutritional care. Additional research should focus on the applicability of current guidelines and evidence for nutrition therapy in populations with obesity, especially in the setting of critical illness.

Actively implementing an evidence-based feeding guideline for critically ill patients (NEED): a multicenter, cluster-randomized, controlled trial.

BACKGROUND: Previous cluster-randomized controlled trials evaluating the impact of implementing evidence-based guidelines for nutrition therapy in critical illness do not consistently demonstrate patient benefits. A large-scale, sufficiently powered study is therefore warranted to ascertain the effects of guideline implementation on patient-centered outcomes. METHODS: We conducted a multicenter, cluster-randomized, parallel-controlled trial in intensive care units (ICUs) across China. We developed an evidence-based feeding guideline. ICUs randomly allocated to the guideline group formed a local "intervention team", which actively implemented the guideline using standardized educational materials, a graphical feeding protocol, and live online education outreach meetings conducted by members of the study management committee. ICUs assigned to the control group remained unaware of the guideline content. All ICUs enrolled patients who were expected to stay in the ICU longer than seven days. The primary outcome was all-cause mortality within 28 days of enrollment. RESULTS: Forty-eight ICUs were randomized to the guideline group and 49 to the control group. From March 2018 to July 2019, the guideline ICUs enrolled 1399 patients, and the control ICUs enrolled 1373 patients. Implementation of the guideline resulted in significantly earlier EN initiation (1.20 vs. 1.55 mean days to initiation of EN; difference - 0.40 [95% CI - 0.71 to - 0.09]; P = 0.01) and delayed PN initiation (1.29 vs. 0.80 mean days to start of PN; difference 1.06 [95% CI 0.44 to 1.67]; P = 0.001). There was no significant difference in 28-day mortality (14.2% vs. 15.2%; difference - 1.6% [95% CI - 4.3% to 1.2%]; P = 0.42) between groups. CONCLUSIONS: In this large-scale, multicenter trial, active implementation of an evidence-based feeding guideline reduced the time to commencement of EN and overall PN use but did not translate to a reduction in mortality from critical illness. TRIAL REGISTRATION: ISRCTN, ISRCTN12233792 . Registered November 20th, 2017.

Case series of four secondary mucormycosis infections in COVID-19 patients, the Netherlands, December 2020 to May 2021.

We describe four secondary fungal infections caused by Mucorales species in COVID-19 patients. Three COVID-19 associated mucormycosis (CAM) occurred in ICU, one outside ICU. All were men aged > 50 years, three died. Clinical presentations included pulmonary, rhino-orbital cerebral and disseminated infection. Infections occurred in patients with and without diabetes mellitus. CAM is an emerging disease and our observations underscore the need to be aware of invasive mucormycosis, including in COVID-19 patients without (poorly controlled) diabetes mellitus and outside ICU.

Exposure Variability and Target Attainment of Vancomycin: A Systematic Review Comparing Intermittent and Continuous Infusion.

BACKGROUND: Studies comparing the clinical outcomes between vancomycin intermittent infusion (InI) and continuous infusion (CoI) treated patients are generally underpowered. Moreover, due to large differences in the design and efficacy end points in these studies, a meta-analysis of the currently available data is not feasible. Therefore, this systematic review aimed to compare the exposure variability and target attainment with vancomycin during InI and CoI. PATIENTS AND METHODS: A literature search was performed, and clinical studies reporting on vancomycin-treated populations were selected. After exclusion of reviews, case reports, and articles not published in the English language, 505 articles were screened for reported data on vancomycin serum concentrations. A total of 34 studies were included in the review. Relative standard deviations reported in the included studies were assessed, and vancomycin serum concentration variability and target attainment were compared between vancomycin InI and CoI. RESULTS: The variability in serum concentrations was significantly larger for InI than for CoI (relative standard deviations 46.5% and 32.1%, respectively; P = 0.001). Notably, variability appeared to be independent of the study population or design. Studies directly comparing target attainment between both modes of administration denoted higher and faster target attainment with CoI in all instances. CONCLUSIONS: In conclusion, CoI was associated with lower variabilities in the serum concentration and favorable target attainment rates compared with InI. These findings are important because vancomycin exposure is considered a major predictor of the patients' clinical outcomes. However, the role of lower serum concentration variability and higher target attainment rates in achieving better clinical outcomes needs to be evaluated in patients treated with vancomycin CoI compared with InI.

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.

Is refeeding syndrome relevant for critically ill patients?

PURPOSE OF REVIEW: To summarize recent relevant studies regarding refeeding syndrome (RFS) in critically ill patients and provide recommendations for clinical practice. RECENT FINDINGS: Recent knowledge regarding epidemiology of refeeding syndrome among critically ill patients, how to identify ICU patients at risk, and strategies to reduce the potential negative impact on outcome are discussed. SUMMARY: RFS is a potentially fatal acute metabolic derangement that ultimately can result in marked morbidity and even mortality. These metabolic derangements in ICU patients differ from otherwise healthy patients with RFS, as there is lack of anabolism. This is because of external stressors inducing a hypercatabolic response among other reasons also reflected by persistent high glucagon despite initiation of feeding. Lack of a proper uniform definition complicates diagnosis and research of RFS. However, refeeding hypophosphatemia is commonly encountered during critical illness. The correlations between risk factors proposed by international guidelines and the occurrence of RFS in ICU patients remains unclear. Therefore, regular phosphate monitoring is recommended. Based on recent trials among critically ill patients, only treatment with supplementation of electrolytes and vitamins seems not sufficient. In addition, caloric restriction for several days and gradual increase of caloric intake over days is recommendable.

Changing paradigms in metabolic support and nutrition therapy during critical illness.

PURPOSE OF REVIEW: To summarize the most recent advances in acute metabolic care and critical care nutrition. RECENT FINDINGS: Recent research has demonstrated unknown consequences of high protein and amino acid administration in the early phase of ICU stay associated with dysregulated glucagon release leading to hepatic amino acid breakdown and suggested adverse effects on autophagy and long-term outcome. Progress has been made to measure body composition in the ICU. Refeeding hypophosphatemia and refeeding syndrome are common during critical illness, phosphate monitoring is essential after the start of nutrition therapy, and caloric restriction is recommendable in these patients.In recent studies, enteral nutrition is no longer superior to parenteral nutrition and signals of harm using the enteral route in shock have been suggested. However, during extracorporeal life support, enteral nutrition seems well tolerated. Intermittent or bolus enteral feeding seems an exciting concept concerning its potential anabolic effects. Studies on vitamin C, thiamine, and corticosteroid combinations suggest potential to improve outcome. SUMMARY: These new findings will probably change the practice of metabolic and nutrition therapy in critical illness and challenge paradigms advocated for long.

Refeeding syndrome: relevance for the critically ill patient.

PURPOSE OF REVIEW: To provide an overview of recent findings concerning refeeding syndrome (RFS) among critically ill patients and recommendations for daily practice. RECENT FINDINGS: Recent literature shows that RFS is common among critically ill ventilated patients. Usual risk factors for non-ICU patients addressed on ICU admission do not identify patients developing RFS. A marked drop of phosphate levels (>0.16 mmol/l) from normal levels within 72 h of commencement of feeding, selects patients that benefit from hypocaloric or restricted caloric intake for at least 48 h resulting in lower long-term mortality. SUMMARY: RFS is a potentially life-threatening condition induced by initiation of feeding after a period of starvation. Although a uniform definition is lacking, most definitions comprise a complex constellation of laboratory markers (i.e. hypophosphatemia, hypokalemia, hypomagnesemia) or clinical symptoms, including cardiac and pulmonary failure. Recent studies show that low caloric intake results in lower mortality rates in critically ill RFS patients compared with RFS patients on full nutritional support. Therefore, standard monitoring of RFS-markers (especially serum phosphate) and caloric restriction when RFS is diagnosed should be considered. Furthermore, standard therapy with thiamin and electrolyte supplementation is essential.

Very high intact-protein formula successfully provides protein intake according to nutritional recommendations in overweight critically ill patients: a double-blind randomized trial.

BACKGROUND: Optimal energy and protein provision through enteral nutrition is essential for critically ill patients. However, in clinical practice, the intake achieved is often far below the recommended targets. Because no polymeric formula with sufficient protein content is available, adequate protein intake can be achieved only by supplemental amino acids or semi-elemental formula administration. In the present study, we investigated whether protein intake can be increased with a new, very high intact-protein formula (VHPF) for enteral feeding. METHODS: In this randomized, controlled, double-blind, multicenter trial, 44 overweight (body mass index ≥ 25 kg/m2) intensive care unit patients received either a VHPF (8 g/100 kcal) or a commercially available standard high protein formula (SHPF) (5 g/100 kcal). Protein and energy intake, gastrointestinal tolerance (gastric residual volume, vomiting, diarrhea, and constipation), adverse events, and serious adverse events were recorded. Total serum amino acid levels were measured at baseline and day 5. RESULTS: The primary outcome, protein intake at day 5, was 1.49 g/kg body weight (95% CI 1.21-1.78) and 0.76 g/kg body weight (95% CI 0.49-1.03, P < 0.001) for VHPF and SHPF, respectively. Daily protein intake was statistically significantly higher in the VHPF group compared with the SHPF group from day 2 to day 10. Protein intake in the VHPF group as a percentage of target (1.5 g/kg ideal body weight) was 74.7% (IQR 53.2-87.6%) and 111.6% (IQR 51.7-130.7%) during days 1-3 and days 4-10, respectively. Serum amino acid concentrations were higher at day 5 in the VHPF group than in the SHPF group (P = 0.031). No differences were found in energy intake, measures of gastrointestinal tolerance, and safety. CONCLUSIONS: Enteral feeding with VHPF (8 g/100 kcal) resulted in higher protein intake and plasma amino acid concentrations than an isocaloric SHPF (5 g/100 kcal), without an increase in energy intake. This VHPF facilitates feeding according to nutritional guidelines and is suitable as a first-line nutritional treatment for critically ill overweight patients. TRIAL REGISTRATION: Netherlands Trial Register, NTR5643 . Registered on 2 February 2016.

Nutrition in the ICU: new trends versus old-fashioned standard enteral feeding?

PURPOSE OF REVIEW: The narrative review aims to summarize the relevant studies from the last 2 years and provide contextual information to understand findings. RECENT FINDINGS: Recent ICU studies have provided insight in the pathophysiology and time course of catabolism, anabolic resistance, and metabolic and endocrine derangements interacting with the provision of calories and proteins.Early provision of high protein intake and caloric overfeeding may confer harm. Refeeding syndrome warrants caloric restriction and to identify patients at risk phosphate monitoring is mandatory.Infectious complications of parenteral nutrition are associated with overfeeding. In recent studies enteral nutrition is no longer superior over parenteral nutrition.Previously reported benefits of glutamine, selenium, and fish oil seem to have vanished in recent studies; however, studies on vitamin C, thiamine, and corticosteroid combinations show promising results. SUMMARY: Studies from the last 2 years will have marked impact on future nutritional support strategies and practice guidelines for critical care nutrition as they challenge several old-fashioned concepts.

Capturing early signs of deterioration: the dutch-early-nurse-worry-indicator-score and its value in the Rapid Response System.

AIMS AND OBJECTIVES: To determine the predictive value of individual and combined dutch-early-nurse-worry-indicator-score indicators at various Early Warning Score levels, differentiating between Early Warning Scores reaching the trigger threshold to call a rapid response team and Early Warning Score levels not reaching this point. BACKGROUND: Dutch-early-nurse-worry-indicator-score comprises nine indicators underlying nurses' 'worry' about a patient's condition. All indicators independently show significant association with unplanned intensive care/high dependency unit admission or unexpected mortality. Prediction of this outcome improved by adding the dutch-early-nurse-worry-indicator-score indicators to an Early Warning Score based on vital signs. DESIGN: An observational cohort study was conducted on three surgical wards in a tertiary university-affiliated teaching hospital. METHODS: Included were surgical, native-speaking, adult patients. Nurses scored presence of 'worry' and/or dutch-early-nurse-worry-indicator-score indicators every shift or when worried. Vital signs were measured according to the prevailing protocol. Unplanned intensive care/high dependency unit admission or unexpected mortality was the composite endpoint. Percentages of 'worry' and dutch-early-nurse-worry-indicator-score indicators were calculated at various Early Warning Score levels in control and event groups. Entering all dutch-early-nurse-worry-indicator-score indicators in a multiple logistic regression analysis, we calculated a weighted score and calculated sensitivity, specificity, positive predicted value and negative predicted value for each possible total score. RESULTS: In 3522 patients, 102 (2·9%) had an unplanned intensive care/high dependency unit admissions (n = 97) or unexpected mortality (n = 5). Patients with such events and only slightly changed vital signs had significantly higher percentages of 'worry' and dutch-early-nurse-worry-indicator-score indicators expressed than patients in the control group. Increasing number of dutch-early-nurse-worry-indicator-score indicators showed higher positive predictive values. CONCLUSIONS: Dutch-early-nurse-worry-indicator-score indicators alert in an early stage of deterioration, before reaching the trigger threshold to call a rapid response team and can improve interdisciplinary communication on surgical wards during regular rounds, and when calling for assistance. RELEVANCE TO CLINICAL PRACTICE: Dutch-early-nurse-worry-indicator-score structures communication and recording of signs known to be associated with a decline in a patient's condition and can empower nurses to call assistance on the 'worry' criterion in an early stage of deterioration.

Nutrition in the critically ill patient.

PURPOSE OF REVIEW: To summarize recent relevant studies regarding nutrition during critical illness and provide recommendations for clinical practice. RECENT FINDINGS: Recently acquired knowledge regarding nutritional status and risk assessment, body composition, gastric residual volume, prokinetics, tube positioning, enteral vs parenteral nutrition, nutritional dose and timing of initiation, pharmaconutrition, dysbiosis and probiotics are discussed. SUMMARY: Body composition especially lean body mass is associated with clinical outcomes. The modified NUTrition Risk in the Critically ill score was validated for nutritional risk assessment and identifies patients that benefit from higher nutritional intake; however, caloric restriction decreases mortality in refeeding syndrome. Gastric residual volume monitoring is debated, as abandoning its application doesn't worsen outcome. There is no consensus regarding benefits of gastric vs postpyloric tube placement. Current prokinetics temporarily reduce feeding intolerance, new prokinetics are developed. Enteral remains preferable over parenteral nutrition, although no inferiority of parenteral nutrition is reported in recent studies. Studies imply no harm of hypocaloric feeding when protein requirements are met. Optimal protein provision may be more important than caloric adequacy. Pharmaconutrition confers no superior outcomes and may even confer harm. Dysbiosis is frequently encountered and associated with worse outcomes. Probiotics reduce infectious complications, but not mortality, and may contribute to earlier recovery of gut function.