Vitamin K: a potential missing link in critical illness-a scoping review.

BACKGROUND: Vitamin K is essential for numerous physiological processes, including coagulation, bone metabolism, tissue calcification, and antioxidant activity. Deficiency, prevalent in critically ill ICU patients, impacts coagulation and increases the risk of bleeding and other complications. This review aims to elucidate the metabolism of vitamin K in the context of critical illness and identify a potential therapeutic approach. METHODS: In December 2023, a scoping review was conducted using the PRISMA Extension for Scoping Reviews. Literature was searched in PubMed, Embase, and Cochrane databases without restrictions. Inclusion criteria were studies on adult ICU patients discussing vitamin K deficiency and/or supplementation. RESULTS: A total of 1712 articles were screened, and 13 met the inclusion criteria. Vitamin K deficiency in ICU patients is linked to malnutrition, impaired absorption, antibiotic use, increased turnover, and genetic factors. Observational studies show higher PIVKA-II levels in ICU patients, indicating reduced vitamin K status. Risk factors include inadequate intake, disrupted absorption, and increased physiological demands. Supplementation studies suggest vitamin K can improve status but not normalize it completely. Vitamin K deficiency may correlate with prolonged ICU stays, mechanical ventilation, and increased mortality. Factors such as genetic polymorphisms and disrupted microbiomes also contribute to deficiency, underscoring the need for individualized nutritional strategies and further research on optimal supplementation dosages and administration routes. CONCLUSIONS: Addressing vitamin K deficiency in ICU patients is crucial for mitigating risks associated with critical illness, yet optimal management strategies require further investigation. IMPACT RESEARCH: To the best of our knowledge, this review is the first to address the prevalence and progression of vitamin K deficiency in critically ill patients. It guides clinicians in diagnosing and managing vitamin K deficiency in intensive care and suggests practical strategies for supplementing vitamin K in critically ill patients. This review provides a comprehensive overview of the existing literature, and serves as a valuable resource for clinicians, researchers, and policymakers in critical care medicine.

Management of hypocalcaemia in the critically ill.

PURPOSE OF REVIEW: To better understand the established associations between hypocalcaemia and clinical outcomes, we synopsize the mechanisms involved in hypocalcaemia in the critically ill. We also provide an overview of the current evidence on managing hypocalcaemia in critical illness. RECENT FINDINGS: Hypocalcaemia is reported to occur in 55-85% of ICU patients. It appears to be associated with poor outcomes. It appears to be associated with poor outcomes, but it may be a marker rather than a direct cause of disease severity. The recommendations to correct calcium in major bleeding are found on weak evidence and require further exploration by a randomized controlled trial (RCT). Calcium administration in cardiac arrest has shown no benefit and may provoke harm. In addition, no RCT has assessed the risks and benefits of calcium supplementation in critically ill hypocalcemic patients. Several recent studies conclude that it may even harm septic ICU patients. These observations are supported by evidence that septic patients using calcium channel blockers may have better outcomes. SUMMARY: Hypocalcaemia is common in critically ill patients. Direct evidence that calcium supplementation improves their outcomes is lacking, and there is even some indication that it may be detrimental. Prospective studies are required to elucidate the risks and benefits, and the pathophysiological mechanisms involved.

Current insights in ICU nutrition: tailored nutrition.

PURPOSE OF REVIEW: To summarize recent research on critical care nutrition focusing on the optimal composition, timing, and monitoring of enteral feeding strategies for (post)-ICU patients. We provide new insights on energy and protein recommendations, feeding intolerance, and describe nutritional practices for coronavirus disease 2019 ICU patients. RECENT FINDINGS: The use of indirect calorimetry to establish individual energy requirements for ICU patients is considered the gold standard. The limited research on optimal feeding targets in the early phase of critical illness suggests avoiding overfeeding. Protein provision based upon the absolute lean body mass is rational. Therefore, body composition measurements should be considered. Body impedance analysis and muscle ultrasound seem reliable, affordable, and accessible methods to assess body composition at the bedside. There is inadequate evidence to change our practice of continuous enteral feeding into intermittent feeding. Finally, severe acute respiratory syndrome coronavirus 2 patients are prone to underfeeding due to hypermetabolism and should be closely monitored. SUMMARY: Nutritional therapy should be adapted to the patient's characteristics, diagnosis, and state of metabolism during ICU stay and convalescence. A personalized nutrition plan may prevent harmful over- or underfeeding and attenuate muscle loss. Despite novel insights, more research is warranted into tailored nutrition strategies during critical illness and convalescence.

Poor physical recovery after critical illness: incidence, features, risk factors, pathophysiology, and evidence-based therapies.

PURPOSE OF REVIEW: To summarize the incidence, features, pathogenesis, risk factors, and evidence-based therapies of prolonged intensive care unit (ICU) acquired weakness (ICU-AW). We aim to provide an updated overview on aspects of poor physical recovery following critical illness. RECENT FINDINGS: New physical problems after ICU survival, such as muscle weakness, weakened condition, and reduced exercise capacity, are the most frequently encountered limitations of patients with postintensive care syndrome. Disabilities may persist for months to years and frequently do not fully recover. Hormonal and mitochondrial disturbances, impaired muscle regeneration due to injured satellite cells and epigenetic differences may be involved in sustained ICU-AW. Although demographics and ICU treatment factors appear essential determinants for physical recovery, pre-ICU health status is also crucial. Currently, no effective treatments are available. Early mobilization in the ICU may improve physical outcomes at ICU-discharge, but there is no evidence for benefit on long-term physical recovery. SUMMARY: Impaired physical recovery is observed frequently among ICU survivors. The pre-ICU health status, demographic, and ICU treatment factors appear to be important determinants for physical convalescence during the post-ICU phase. The pathophysiological mechanisms involved are poorly understood, thereby resulting in exiguous evidence-based treatment strategies to date.

Electrolyte disorders during the initiation of nutrition therapy in the ICU.

PURPOSE OF REVIEW: To summarize recent evidence on prevalence, risk factors, significance, treatment, and prevention of electrolyte disorders in critically ill with a specific focus on disorders during the initiation of nutrition. RECENT FINDINGS: Electrolyte disturbances appear to occur often during critical illness, and most of them seem to be associated with impaired outcome. However, a recent systematic review indicated insufficient evidence to answer clinically relevant questions regarding hypophosphatemia. Similar questions (which thresholds of serum levels are clinically relevant; how serum levels should be corrected and how do different correction regimens/approaches influence outcome) are not clearly answered also for other electrolytes. The most crucial feature of electrolyte disturbances related to feeding is refeeding syndrome. Recent evidence supports that additionally to the correction of electrolyte levels, a temporary restriction of calories (reducing the magnitude of this metabolic feature, including electrolyte shifts) may help to improve outcome. SUMMARY: Diverse electrolyte disorders often occur in critically ill patients. Hypophosphatemia, hypokalemia, and hypomagnesemia that are encountered after initiation of feeding identify refeeding syndrome. Along with correction of electrolytes, reduction of caloric intake may improve the outcome of the refeeding syndrome.

Bioelectric impedance analysis for body composition measurement and other potential clinical applications in critical illness.

PURPOSE OF REVIEW: Insight into body composition is of great value in the ICU. Bioelectric impedance analysis (BIA) is the most applicable bedside technique. However, bioimpedance has not been validated in the critically ill, and the interpretation of the measurements poses challenges. This review discusses the potential clinical applications of BIA and explores caveats and solutions to its use in the intensive care setting. RECENT FINDINGS: A correlation is repeatedly found between raw impedance parameters, fluid ratios, overhydration, and adverse outcome of critical illness. However, cut-off and reference values remain elusive. Experience with BIA-guided fluid management in the ICU is limited. BIA-derived muscle mass appears a promising biomarker for sarcopenia, correlating well with CT-analysis. Body cell mass and fat-free mass provide potential use in estimation of metabolic rate, protein requirements and pharmacokinetics. Several methods of reducing bias in BIA parameters in critical illness require validation. SUMMARY: There are currently too many uncertainties and discrepancies regarding interpretation of bioimpedance in critical illness, to justify therapeutic consequences. However, there are several promising areas of research, concerning some of the most urgent clinical problems in intensive care, emphasizing the need to evaluate further the use and interpretation of bioimpedance in the intensive care setting.

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

PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: 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.

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.

Do we need new prokinetics to reduce enteral feeding intolerance during critical illness?

Gastrointestinal feeding intolerance and critical illness-associated gastric motility dysfunction are common. Although recent guidelines recommend not interrupting gastric feeding when gastric residual volume (GRV) is lower than 500 mL or to completely abandon measurement of GRV, it may seem that the relevance of prokinetics is reduced.In patients at risk for aspiration and in multimodal strategies to enhance feeding performance, however, use of prokinetics is still advocated. Metoclopramide and erythromycin are commonly used promotility agents, although with relevant side effects.Potential targets for new agents and early study results are addressed.

Early protein delivery in critically ill patients with acute kidney injury: post hoc analysis of a multicenter cluster-randomized controlled trial.

Background: There is controversy over the optimal early protein delivery in critically ill patients with acute kidney injury (AKI). This study aims to evaluate whether the association between early protein delivery and 28-day mortality was impacted by the presence of AKI in critically ill patients. Methods: This is a post hoc analysis of data from a multicenter cluster-randomised controlled trial enrolling newly admitted critically ill patients (n = 2772). Participants without chronic kidney disease and with complete data concerning baseline renal function were included in this study. The primary outcome was 28-day mortality. Cox proportional hazards models were used to analyze the association between early protein delivery, reflected by mean protein delivery from day 3-5 after enrollment, 28-day mortality and whether baseline AKI stages interacted with this association. Results: Overall, 2552 patients were included, among whom 567 (22.2%) had AKI at enrollment (111 stage I, 87 stage II, 369 stage III). Mean early protein delivery was 0.60 ± 0.38 g/kg/day among the study patients. In the overall study cohort, each 0.1 g/kg/day increase in protein delivery was associated with a 5% reduction in 28-day mortality[hazard ratio (HR) = 0.95; 95% confidence interval (CI) 0.92-0.98, p < 0.001]. The association between early protein delivery and 28-day mortality significantly interacted with baseline AKI stages (adjusted interaction p = 0.028). Each 0.1 g/kg/day increase in early protein delivery was associated with a 4% reduction in 28-day mortality (HR = 0.96; 95%CI 0.92-0.99, p = 0.011) among patients without AKI and 9% (HR = 0.91; 95%CI 0.84-0.99, p = 0.021) among those with AKI stage III. However, such associations cannot be observed among patients with AKI stages I and II. Conclusions: Increased early protein delivery (up to close to the guideline recommendation) was associated with reduced 28-day mortality in critically ill patients without AKI and with AKI stage III, but not in those with AKI stage I or II.

Physical recovery of COVID-19 pneumosepsis intensive care survivors compared with non-COVID pneumosepsis intensive care survivors during post-intensive care hospitalization: The RECOVID retrospective cohort study.

BACKGROUND: Coronavirusdisease 2019 (COVID-19) pneumosepsis survivors are at a high risk of developing intensive care unit (ICU)-acquired weakness (ICUAW) because of high incidence of acute respiratory distress syndrome and the common need for prolonged invasive ventilation. It remains unknown whether regular postpneumosepsis physical rehabilitation strategies are suitable for this extraordinary patient category. METHODS: We retrospectively compared the physical recovery of COVID-19 and non-COVID pneumosepsis ICU survivors during post-ICU hospitalization, defined as the difference in performance on the Medical Research Council Sum-Score (MRC-SS), Chelsea Critical Care Physical Assessment tool (CPAx), and percentage of predicted handgrip strength (POP-HGS). An analysis of covariance model was built using age, sex, Barthel index, body mass index, admission Acute Physiology And Chronic Health Evaluation II score, adequacy of protein delivery during ICU stay, and ward length of stay as covariates. RESULTS: Thirty-five COVID-19 ICU patients could be compared with 21 non-COVID pneumosepsis ICU survivors. All patients scored ≤48 on the MRC-SS at ICU discharge, indicating ICUAW. When controlling for covariates, COVID-19 patients performed worse on all physical assessments upon ICU discharge, but had improved more at hospital discharge on the MRC-SS (ɳ2 = 0.214, P =.002) and CPAx (ɳ2 = 0.153, P =.011). POP-HGS remained lower in COVID-19 patients throughout hospital stay. CONCLUSION: COVID-19 ICU survivors are vulnerable to ICUAW, but they show better tendency towards physical rehabilitation than non-COVID pneumosepsis ICU survivors during the post-ICU hospitalization period regarding MRC-SS and CPAx. COVID-19 ICU patients might benefit from early, more intensive physical therapy.

Energy expenditure and indirect calorimetry in critical illness and convalescence: current evidence and practical considerations.

The use of indirect calorimetry is strongly recommended to guide nutrition therapy in critically ill patients, preventing the detrimental effects of under- and overfeeding. However, the course of energy expenditure is complex, and clinical studies on indirect calorimetry during critical illness and convalescence are scarce. Energy expenditure is influenced by many individual and iatrogenic factors and different metabolic phases of critical illness and convalescence. In the first days, energy production from endogenous sources appears to be increased due to a catabolic state and is likely near-sufficient to meet energy requirements. Full nutrition support in this phase may lead to overfeeding as exogenous nutrition cannot abolish this endogenous energy production, and mitochondria are unable to process the excess substrate. However, energy expenditure is reported to increase hereafter and is still shown to be elevated 3 weeks after ICU admission, when endogenous energy production is reduced, and exogenous nutrition support is indispensable. Indirect calorimetry is the gold standard for bedside calculation of energy expenditure. However, the superiority of IC-guided nutritional therapy has not yet been unequivocally proven in clinical trials and many practical aspects and pitfalls should be taken into account when measuring energy expenditure in critically ill patients. Furthermore, the contribution of endogenously produced energy cannot be measured. Nevertheless, routine use of indirect calorimetry to aid personalized nutrition has strong potential to improve nutritional status and consequently, the long-term outcome of critically ill patients.

Association of bioelectric impedance analysis body composition and disease severity in COVID-19 hospital ward and ICU patients: The BIAC-19 study.

BACKGROUND: The current severe acute respiratory syndrome coronavirus 2 pandemic is unprecedented in its impact. It is essential to shed light on patient characteristics that predispose to a more severe disease course. Obesity, defined as a BMI>30 kg/m2, is suggested to be one of these characteristics. However, BMI does not differentiate between fat mass and lean body mass, or the distribution of fat tissue. The aim of the present study was to assess the body composition of COVID-19 patients admitted to the ward or the ICU and identify any associations with severity of disease. METHODS: We performed an observational cross-sectional cohort study. Bioelectric impedance analysis was conducted amongst all confirmed COVID-19 patients admitted to the ward or ICU of our hospital in the Netherlands, between April 10 and 17, 2020. Body water measurements and derived values were recalculated to dry weight, using a standard ratio of extracellular water to total body water of 0.38. Data were compared between the ward and ICU patients, and regression models were used to assess the associations between baseline characteristics, body composition, and several indicators of disease severity, including a composite score composed of mortality, morbidity, and ICU admission. RESULTS: Fifty-four patients were included, of which 30 in the ward and 24 in the ICU. The mean age was 67 years (95%-CI 64-71), and 34 (63%) were male. Mean BMI was 29.7 (95%-CI 28.2-31.1) kg/m2 and did not differ between groups. Body composition values were not independently associated with disease severity. In multiple logistic regression analyses, a low phase angle was associated with COVID-19 severity in the composite score (OR 0.299, p = 0.046). CONCLUSION: We found no significant associations between body composition, including fat mass, visceral fat area, and fat-free mass, and disease severity in our population of generally overweight COVID-19 patients. A lower phase angle did increase the odds of severe COVID-19. We believe that factors other than body composition play a more critical role in the development of severe COVID-19.

Association of PROtein and CAloric Intake and Clinical Outcomes in Adult SEPTic and Non-Septic ICU Patients on Prolonged Mechanical Ventilation: The PROCASEPT Retrospective Study.

BACKGROUND: The optimal nutritional support for critically ill septic patients remains unknown. This study evaluates the associations of macronutrient intake during the first week of intensive care unit (ICU) admission and long-term clinical outcomes in septic and non-septic patients. METHODS: Prolonged mechanically ventilated patients were retrospectively studied. The association of protein (low: <0.8 g/kg/d, medium: 0.8-1.2 g/kg/d, high >1.2 g/kg/d) and energy intake (<80%, 80%-110%, 110% of target) during days 1-3 and 4-7 after ICU admission and 6-month mortality was analyzed for septic and non-septic patients separately. RESULTS: A total of 423 patients were investigated. Of these, 297 had sepsis. In the sepsis group, medium protein intake at days 4-7 was associated with lower 6-month mortality (hazard ratio [HR]: 0.646, 95% confidence interval [CI]: 0.418-0.996, P=0.048) compared with high intake. In the non-sepsis group, early high and late low protein intake were associated with higher 6-month mortality (HR: 3.902, 95% CI: 1.505-10.115, P=0.005; HR: 2.642, 95% CI: 1.128-6.189, P=0.025) compared with low and high protein intake, respectively. For energy intake, late energy intake of >110% was associated with decreased mortality in septic patients (HR: 0.400, 95% CI: 0.222-0.721, P=0.002), whereas in non-septic patients, late medium energy intake (80%-110%) was associated with better survival (HR: 0.379, 95% CI: 0.175-0.820, P=0.014), both compared with low energy intake. CONCLUSION: Divergent associations of macronutrient intake were found; early high protein intake in non-septic patients, but not in septic patients, was found to be associated with higher 6-month mortality.

The Effect of Nutrition on Early Stress-Induced Hyperglycemia, Serum Insulin Levels, and Exogenous Insulin Administration in Critically Ill Patients With Septic Shock: A Prospective Observational Study.

BACKGROUND: Stress-induced hyperglycemia is common among septic shock patients. Nutritional support influences glucose homeostasis but this effect has never been studied in septic shock. We aimed to determine the course of hyperglycemia and serum insulin levels in critically ill septic shock patients and to address the effects of caloric intake on glycemia, insulin levels, and exogenous insulin requirements. METHODS: A prospective observational study of 24 ventilated septic shock patients during 72 h after ICU admission. Every 4 h nutritional variables, exogenous insulin administration, serum insulin, and glucose levels were recorded. RESULTS: Stress-induced hyperglycemia was found in 96.2% of patients. Exogenous insulin requirements increased gradually and were most pronounced at 36 h (mean 4.64 IU/h). Total serum insulin levels were lowest at the point of most exogenous insulin requirements (mean 2.75 mIU/L). Total caloric intake and insulin requirements were positively associated (Pearson correlation coefficient 0.210). CONCLUSIONS: In patients with septic shock marked reduced serum insulin levels can be observed during the first 36 h after intensive care unit (ICU) admission that have to be compensated by exogenous insulin administration, a phenomenon gradually improving after 36 h. Feeding is positively associated with exogenous insulin requirements. These results suggest that strategies to manage stress-induced hyperglycemia in patients with septic shock should consider frequent glycemic monitoring, conservative insulin dosing to prevent hypoglycemia when insulin resistance disappears, and slow progressive nutrition support during the early ICU phase as caloric loading may worsen hyperglycemia. This approach may attenuate the risk of glucose variability, hypo- and hyperglycemia and associated poor outcomes.