Micronutrient deficiencies in critical illness.

BACKGROUND & AIMS: Low micronutrient levels in critical illness have been reported in multiple studies. Because of the antioxidant properties of various micronutrients, micronutrient deficiency may augment oxidative stress in critical illness. However, it remains unclear whether micronutrient concentrations in ICU patients are different from those in healthy age-matched controls. It is also unclear whether micronutrient deficiency develops, worsens, or resolves during ICU admission without supplementation. METHODS: We prospectively studied a cohort of adult critically ill patients. Micronutrient levels, including selenium, ß-carotene, vitamin C, E, B1 and B6 were measured repeatedly during the first week of ICU admission. We compared the micronutrient concentrations at ICU admission to those of healthy age-matched controls. In addition, associations between micronutrient concentrations with severity of illness, inflammation and micronutrient intake were investigated. RESULTS: Micronutrient blood concentrations were obtained from 24 critically ill adults and 21 age-matched healthy controls. The mean micronutrient levels at admission in the ICU patients were: selenium 0.52 µmol/l, ß-carotene 0.17 µmol/l, vitamin C 21.5 µmol/l, vitamin E 20.3 µmol/l, vitamin B1 129.5 nmol/l and vitamin B6 41.0 nmol/l. In the healthy controls micronutrient levels of selenium (0.90 µmol/l), ß-carotene (0.50 µmol/l), vitamin C (45 µmol/l) and vitamin E (35.5 µmol/l) were significantly higher, while vitamin B1 (122 nmol/l) and B6 (44 nmol/l) were not significantly different between patients and controls. Selenium, vitamin B1 and vitamin B6 levels remained stable during ICU admission. Vitamin C levels dropped significantly until day 5 (p < 0.01). Vitamin E and ß-carotene levels increased significantly on days 5-7 and day 7, respectively (p < 0.01). Micronutrient levels were not associated with severity of illness, CRP or micronutrient intake during the admission. CONCLUSIONS: At admission, ICU patients already had lower plasma levels of selenium, ß-carotene, vitamin C and vitamin E than healthy controls. Vitamin C levels dropped significantly during the first days of ICU admission, while ß-carotene and vitamin E levels increased after 5-7 days. No association between micronutrient levels and severity of illness, C-reactive protein (CRP) or micronutrient intake was found. Progressive enteral tube feeding containing vitamins and trace elements does not normalize plasma levels in the first week of ICU stay. This was a hypothesis generating study and more investigation in a larger more diverse sample is needed.

Resting energy expenditure by indirect calorimetry versus the ventilator-VCO2 derived method in critically ill patients: The DREAM-VCO2 prospective comparative study.

BACKGROUND & AIMS: Both overfeeding and underfeeding of intensive care unit (ICU) patients are associated with worse outcomes. Predictive equations of nutritional requirements, though easily implemented, are highly inaccurate. Ideally, the individual caloric target is based on the frequent assessment of energy expenditure (EE). Indirect calorimetry is considered the gold standard but is not always available. EE estimated by ventilator-derived carbon dioxide consumption (EEVCO2) has been proposed as an alternative to indirect calorimetry, but there is limited evidence to support the use of this method. METHODS: We prospectively studied a cohort of adult critically ill patients requiring mechanical ventilation and artificial nutrition. We aimed to compare the performance of the EEVCO2 with the EE measured by indirect calorimetry through the calculation of bias and precision (accuracy), agreement, reliability and 10% accuracy rates. The effect of including the food quotient (nutrition intake derived respiratory quotient) in contrast to a fixed respiratory quotient (0.86), into the EEVCO2 formula was also evaluated. RESULTS: In 31 mechanically ventilated patients, a total of 414 paired measurements were obtained. The mean estimated EEVCO2 was 2134 kcal/24 h, and the mean estimated EE by indirect calorimetry was 1623 kcal/24 h, depicting a significant bias of 511 kcal (95% CI 467-560, p < 0.001). The precision of EEVCO2 was low (lower and upper limit of agreement -63.1 kcal and 1087. o kcal), the reliability was good (intraclass correlation coefficient 0.613; 95% CI 0.550-0.669, p < 0.001) and the 10% accuracy rate was 7.0%. The food quotient was not significantly different from the respiratory quotient (0.870 vs. 0.878), with a small bias of 0.007 (95% CI 0.000-0.015, p = 0.54), low precision (lower and upper limit of agreement -0.16 and 0.13), poor reliability (intraclass correlation coefficient 0.148; 95% CI 0.053-0.240, p = 0.001) and a 10% accuracy rate of 77.5%. Estimated mean EEVCO2, including the food quotient, was 2120 kcal/24 h, with a significant bias of 496 kcal (95% CI 451-542; p < 0.001) and low precision (lower and upper limit of agreement -157.6 kcal and 1170.3 kcal). The reliability with EE estimated by indirect calorimetry was good (intraclass correlation coefficient 0.610, 95% CI 0.550-0.661, p < 0.001), and the 10% accuracy rate was 9.2%. CONCLUSIONS: EEVCO2, compared with indirect calorimetry, overestimates actual energy expenditure. Although the reliability is acceptable, bias is significant, and the precision and accuracy rates are unacceptably low when the VCO2 method is used. Including the food quotient into the EEVCO2 equation does not improve its performance. Predictive equations, although inaccurate, may even predict energy expenditure better compared with the VCO2-method. Indirect calorimetry remains the gold standard method.

The effect of cisatracurium infusion on the energy expenditure of critically ill patients: an observational cohort study.

BACKGROUND: Both overfeeding and underfeeding of intensive care unit (ICU) patients are associated with worse outcomes. A reliable estimation of the energy expenditure (EE) of ICU patients may help to avoid these phenomena. Several factors that influence EE have been studied previously. However, the effect of neuromuscular blocking agents on EE, which conceptually would lower EE, has not been extensively investigated. METHODS: We studied a cohort of adult critically ill patients requiring invasive mechanical ventilation and treatment with continuous infusion of cisatracurium for at least 12 h. The study aimed to quantify the effect of cisatracurium infusion on EE (primary endpoint). EE was estimated based on ventilator-derived VCO2 (EE in kcal/day = VCO2 × 8.19). A subgroup analysis of septic and non-septic patients was performed. Furthermore, the effects of body temperature and sepsis on EE were evaluated. A secondary endpoint was hypercaloric feeding (> 110% of EE) after cisatracurium infusion. RESULTS: In total, 122 patients were included. Mean EE before cisatracurium infusion was 1974 kcal/day and 1888 kcal/day after cisatracurium infusion. Multivariable analysis showed a significantly lower EE after cisatracurium infusion (MD - 132.0 kcal (95% CI - 212.0 to - 52.0; p = 0.001) in all patients. This difference was statistically significant in both sepsis and non-sepsis patients (p = 0.036 and p = 0.011). Non-sepsis patients had lower EE than sepsis patients (MD - 120.6 kcal; 95% CI - 200.5 to - 40.8, p = 0.003). Body temperature and EE were positively correlated (Spearman's rho = 0.486, p < 0.001). Hypercaloric feeding was observed in 7 patients. CONCLUSIONS: Our data suggest that continuous infusion of cisatracurium in mechanically ventilated ICU patients is associated with a significant reduction in EE, although the magnitude of the effect is small. Sepsis and higher body temperature are associated with increased EE. Cisatracurium infusion is associated with overfeeding in only a minority of patients and therefore, in most patients, no reductions in caloric prescription are necessary.

Timing of PROTein INtake and clinical outcomes of adult critically ill patients on prolonged mechanical VENTilation: The PROTINVENT retrospective study.

BACKGROUND & AIMS: Optimal protein intake during critical illness is unknown. Conflicting results on nutritional support during the first week of ICU stay have been published. We addressed timing of protein intake and outcomes in ICU patients requiring prolonged mechanical ventilation. METHODS: We retrospectively collected nutritional and clinical data on the first 7 days of ICU admission of adult critically ill patients, who were mechanically ventilated in our ICU for at least 7 days and admitted between January 1st 2011 and December 31st 2015. Based on recent literature, patients were divided into 3 protein intake categories, <0.8 g/kg/day, 0.8-1.2 g/kg/day and >1.2 g/kg/day. Our primary aim was to identify the optimum protein dose and timing related to the lowest 6 month mortality. Secondary endpoints were ventilation duration, need for renal replacement therapy (RRT), ICU length of stay (LOS) and mortality and hospital LOS and mortality. RESULTS: In total 455 patients met the inclusion criteria. We found a time-dependent association of protein intake and mortality; low protein intake (<0.8 g/kg/day) before day 3 and high protein intake (>0.8 g/kg/day) after day 3 was associated with lower 6-month mortality, adjusted HR 0.609; 95% CI 0.480-0.772, p < 0.001) compared to patients with overall high protein intake. Lowest 6-month mortality was found when increasing protein intake from <0.8 g/kg/day on day 1-2 to 0.8-1.2 g/kg/day on day 3-5 and >1.2 g/kg/day after day 5. Moreover, overall low protein intake was associated with the highest ICU, in-hospital and 6-month mortality. No differences in ICU LOS, need for RRT or ventilation duration were found. CONCLUSIONS: Our data suggest that although overall low protein intake is associated with the highest mortality risk, high protein intake during the first 3-5 days of ICU stay is also associated with increased long-term mortality. Therefore, timing of high protein intake may be relevant for optimizing ICU, in-hospital and long-term mortality outcomes.

Feeding mitochondria: Potential role of nutritional components to improve critical illness convalescence.

Persistent physical impairment is frequently encountered after critical illness. Recent data point towards mitochondrial dysfunction as an important determinant of this phenomenon. This narrative review provides a comprehensive overview of the present knowledge of mitochondrial function during and after critical illness and the role and potential therapeutic applications of specific micronutrients to restore mitochondrial function. Increased lactate levels and decreased mitochondrial ATP-production are common findings during critical illness and considered to be associated with decreased activity of muscle mitochondrial complexes in the electron transfer system. Adequate nutrient levels are essential for mitochondrial function as several specific micronutrients play crucial roles in energy metabolism and ATP-production. We have addressed the role of B vitamins, ascorbic acid, α-tocopherol, selenium, zinc, coenzyme Q10, caffeine, melatonin, carnitine, nitrate, lipoic acid and taurine in mitochondrial function. B vitamins and lipoic acid are essential in the tricarboxylic acid cycle, while selenium, α-tocopherol, Coenzyme Q10, caffeine, and melatonin are suggested to boost the electron transfer system function. Carnitine is essential for fatty acid beta-oxidation. Selenium is involved in mitochondrial biogenesis. Notwithstanding the documented importance of several nutritional components for optimal mitochondrial function, at present, there are no studies providing directions for optimal requirements during or after critical illness although deficiencies of these specific micronutrients involved in mitochondrial metabolism are common. Considering the interplay between these specific micronutrients, future research should pay more attention to their combined supply to provide guidance for use in clinical practise. REVISION NUMBER: YCLNU-D-17-01092R2.

Impact of caloric intake in critically ill patients with, and without, refeeding syndrome: A retrospective study.

BACKGROUND & AIMS: Refeeding syndrome comprises metabolic disturbances that occur after the reintroduction of feeding after prolonged fasting. Standard care consists of correcting fluid and electrolytes imbalances. Energy intake during refeeding syndrome is heavily debated. This study addresses the effect of caloric intake on outcome during the management of refeeding syndrome. METHODS: A retrospective study among critically ill invasive mechanically ventilated patients admitted for >7 days to a medical-surgical ICU. Refeeding syndrome was diagnosed by the occurrence of new onset hypophosphatemia (<0.65 mmol/l) within 72 h of the start of nutritional support. Primary outcome was 6-month mortality. Secondary outcomes were 3-month mortality, ICU and hospital length of stay and duration of mechanical ventilation. Outcomes of patients with and without refeeding syndrome were compared and subgroup analysis on energy intake within the refeeding population was performed for the duration of survival. RESULTS: Of 337 enrolled patients, 124 (36.8%) developed refeeding syndrome and 213 patients (63.2%) maintained normal serum phosphate levels. Between the two groups, no statistical significant differences in clinical outcomes were observed. Within the refeeding syndrome group, a reduced 6-month mortality risk for low caloric intake (<50% of target) was seen compared with normal intake, adjusted Hazard Ratio 0.39, (95% CI 0.16-0.95, p = 0.037). In this group, low caloric intake was associated with an increased overall survival time at day 180 (153.0 (SE 10.1) vs 119.1 (SE 8.0) days, log-rank p = 0.018). CONCLUSIONS: Refeeding syndrome is common among prolonged mechanically ventilated critically ill patients, however not predictable by baseline characteristics. Among patients that develop refeeding syndrome low caloric intake was associated with a reduction in 6-month mortality risk. This effect was not seen in patients without refeeding syndrome. Findings support caloric restriction in refeeding syndrome during critical illness.

Data on effects, tolerability and safety of Omega-3 Fatty Acids in Enteral Nutrition in the Critically ill.

In addition to the data reported in our systematic review and meta-analysis 'Current Evidence on Omega-3 Fatty Acids in Enteral Nutrition in the Critically ill' we present data on intensive care unit and hospital mortality, age distribution between included studies, tolerability and adverse events of enteral omega-3 supplementation compared with control interventions in the critically ill. Moreover, we report additional analyses on 28-day mortality comparing old versus new studies and high versus low quality trials. Finally, we report baseline and follow-up levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) reported in the trials included in Koekkoek et al. (2018). For further interpretation and discussion we recommend reading our systematic review and meta-analysis Current Evidence on Omega-3 Fatty Acids in Enteral Nutrition in the Critically ill'.

[The acutely ill oncological patient: admit to ICU or not?] / Acuut zieke patiënt met kanker: wel of niet naar IC?

- 5-10% of all oncological patients will be admitted to ICU at some point.- Medical oncological patients are usually admitted due to respiratory insufficiency or sepsis.- Mortality among medical-oncological ICU patients has decreased to an average of 40%, with a wide spread per tumour type.- The main prognostic factors for ICU survival are: clinical condition, severity of the acute condition, tumour type, and some specific oncological conditions.- This article describes directive ICU admission criteria, subdivided into three categories of medical oncological patients. Although not validated, these criteria give guidance to clinicians in deciding whether ICU admission is a responsible course of action.- In patients with an uncertain prognosis an ICU trial can be useful.- ICU admission criteria are largely based on expert opinion, as sufficient scientific evidence is lacking. A multidisciplinary decision process is therefore important.- Ideally, decision-making about ICU treatment should take place at an early stage in primary health care or outpatient clinic; this is called Advance Care Planning.

[Extracorporeal life support for Legionella pneumonia]. / Extracorporele life support bij Legionella-pneumonie.

BACKGROUND: Legionella species cause 5% of all community acquired pneumonias. However, Legionella pneumonia results relatively often in admission to the intensive care unit (ICU). A significant complication is the development of acute respiratory distress syndrome (ARDS). The ICU mortality rate for Legionella pneumonia is > 30% with conventional treatments. CASE DESCRIPTION: A 64-year-old male was admitted to the ICU with respiratory failure due to Legionella pneumonia complicated by ARDS. Despite maximum conventional therapy being given, including lung-protective invasive mechanical ventilation and prone positioning, progressive hypoxaemia persisted. In collaboration with an extracorporeal life support (ECLS) centre, venovenous ECLS was initiated. Pulmonary function recovered and the patient was successfully weaned from VV-ECLS after 17 days. After three months of hospitalisation and rehabilitation, the patient was discharged home and able to perform his activities of daily living without assistance. CONCLUSION: Legionella pneumonia relatively frequently results in ICU admission, and carries a high mortality with conventional treatments. ECLS may offer a solution if conventional therapies are not sufficiently effective.

Antioxidant Vitamins and Trace Elements in Critical Illness.

This comprehensive narrative review summarizes relevant antioxidant mechanisms, the antioxidant status, and effects of supplementation in critically ill patients for the most studied antioxidant vitamins A, C, and E and the enzyme cofactor trace elements selenium and zinc. Over the past 15 years, oxidative stress-mediated cell damage has been recognized to be fundamental to the pathophysiology of various critical illnesses such as acute respiratory distress syndrome, ischemia-reperfusion injury, and multiorgan dysfunction in sepsis. Related to these conditions, low plasma levels of antioxidant enzymes, vitamins, and trace elements have been frequently reported, and thus supplementation seems logical. However, low antioxidant plasma levels per se may not indicate low total body stores as critical illness may induce redistribution of antioxidants. Furthermore, low antioxidant levels may even be beneficial as pro-oxidants are essential in bacterial killing. The reviewed studies in critically ill patients show conflicting results. This may be due to different patient populations, study designs, timing, dosing regimens, and duration of the intervention and outcome measures evaluated. Therefore, at present, it remains unclear whether supplementation of antioxidant micronutrients has any clinical benefit in critically ill patients as some studies show clear benefits, whereas others demonstrate neutral outcomes and even harm. Combination therapy of antioxidants seems logical as they work in synergy and function as elements of the human antioxidant network. Further research should focus on defining the normal antioxidant status for critically ill patients and to study optimal supplement combinations either by nutrition enrichment or by enteral or parenteral pharmacological interventions.

[Shock-induced ischemic optic neuropathy]. / Shockgeïnduceerde ischemische opticusneuropathie.

BACKGROUND: Shock can lead to ischemic injury of organs. Ischemic injury of the optic nerve may even cause blindness. CASE DESCRIPTION: A 61-year-old female patient was admitted to ICU with septic shock. When recovering, she was only able to determine the difference between light and dark; before admission her vision was good. Ophthalmologic examination revealed slow pupillary reflexes and pale, atrophic optic discs. The diagnosis of bilateral shock-induced ischemic optic neuropathy was made. The patient was permanently blind and traumatised by her experiences during her hospital stay when her blindness was not yet recognised. CONCLUSION: Blindness caused by ischemic optic neuropathy is a rare and severe complication of shock that is usually irreversible. Early recognition is important in order to allow appropriate communication with, and approach of the patient to prevent traumatic experiences and promote rehabilitation.