Selenium in intensive care: probably not a magic bullet but an important adjuvant therapy.
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Antioxidants↗
Biomedical subjects
Mette M Berger
Publications and source records attributed to Mette M Berger.
Effects of fish oil on the neuro-endocrine responses to an endotoxin challenge in healthy volunteers.
BACKGROUND & AIMS: Fish oil (FO) has been shown to modulate the acute and chronic inflammatory responses. Endotoxin (LPS) has been shown to mimic several aspects of sepsis. The study aimed at testing the effects of oral FO supplements in healthy subjects submitted to intravenous LPS on systemic and endocrine response. SUBJECTS AND METHODS: Fifteen healthy men (aged 26.0+/-3.1 years, BMI 23.8+/-1.9 kg/m2), were enrolled. Subjects were randomised to 3-4 weeks of oral FO supplementation (7.2 g/day, providing 1.1 g/day of 20:5 (n-3) and 0.7 g/day of 22:6 (n-3) fatty acids) or no supplementation and then submitted to endotoxin challenge: 2 ng/kg of LPS. All subjects were studied twice (placebo and LPS). MEASUREMENTS: vital signs, energy expenditure (EE), glucose and lipid metabolism ((2)H2-glucose), plasma cytokines and stress hormones for 6 h after LPS or placebo. RESULTS: LPS caused cytokine release, fever, increases in heart rate, resting EE and substrate oxidation, plasma glucagon and glucose concentrations; the neuro-endocrine response was characterised by increased plasma stress hormones. FO significantly blunted fever, ACTH and cortisol plasma levels (no effect on cytokine release). FO blunted the peak norepinephrine after LPS. CONCLUSION: FO supplements blunted the endocrine stress response and the increase in body temperature, but had no impact on cytokine production after LPS. These findings conflict with the postulated anti-inflammatory effects of FO on arachidonic acid metabolism and cytokine release. These results suggest that FO may exert beneficial effects in sepsis though non-inflammatory which require further investigations.
Adrenocorticotropic Hormone↗
Nutritional status and food intake in nine patients with chronic low-limb ulcers and pressure ulcers: importance of oral supplements.
OBJECTIVES: Chronic low-limb ulcers and pressure ulcers are a serious and costly issue. Malnutrition is a risk factor. Searching for intervention strategies in elderly patients referred for surgical closure of their ulcers, the trial aimed at investigating the micronutrient status, determining the food intake of such patients, and the role of oral liquid supplements. METHODS: Observational cohort study in 9 patients, starting 5 days prior to surgery until day 10 after surgery. VARIABLES: body mass index (BMI), food intake assessed using standardized meals (energy target 25 kcal/kg/day). Oral liquid supplements were provided between meals. Laboratory: blood count, plasma proteins, antioxidant status, vitamins, Fe, Se, and Zn. RESULTS: The patients were aged 71+/-10 y (mean+/-SD), with a BMI of 23.3+/-3.3. Baseline blood samples showed anemia and strong inflammation in 4 patients: albumin, retinol, and selenium were low; iron and zinc were very low. Food intake was largely variable and covered only about 76% (31-95%) of energy requirements. Breakfast provided 225+/-110, lunch 570+/-215, and dinner 405+/-150 kcal. Supplements were willingly consumed covering 35+/-12% of energy target. While vitamin supply was adequate, selenium and zinc requirements were not met. CONCLUSIONS: Most patients with chronic skin ulcers suffered micronutrient status alterations, and borderline malnutrition. Meals did not cover energy requirements, while oral supplements covered basic micronutrient requirements and compensated for insufficient oral energy and protein intakes, justifying their use in hospitalized elderly patients.
Administration, Oral↗
Impact of a computerized information system on quality of nutritional support in the ICU.
OBJECTIVE: In intensive care units (ICUs), patient outcome depends on quality of nutritional support. We investigated the effect of computerized information systems (CISs) on quality of nutritional support by comparing two ICUs with or without CIS and burned patients before and after CIS implementation. METHODS: Part 1 was a 2-wk prospective survey in two units of a surgical ICU: unit A (11 beds) without CIS and unit B (four beds) with CIS. Part 2 consisted of two 18-mo periods in burn patients before and after CIS implementation. Nurses and doctors belonged to the same team; procedures were identical. A computer page was configured to retrieve data related to nutritional support. RESULTS: A total of 1313 ICU days were analyzed in 109 patients. Patients' characteristics were similar in parts 1 and 2. In part 1, nutritional support was required 38% of days. Nutritional route was similar but data were more frequently missing in unit A. Energy delivery was higher with CIS but below target values in both units (31+/-11% of target in unit A, 77+/-4% in unit B). Computations were incomplete and time consuming for unit A versus B (11+/-2 versus 2+/-1 min/patient, P<0.0001). In part 2, in the 54 burn patients, use of postpyloric feeding tubes and energy delivery increased with CIS, resulting in less weight loss. CONCLUSION: Computerized information systems favored standardization of nutritional care and monitoring, thus decreasing time required for writing and computations. Follow-up was improved and nutrient delivery was closer to target values, thus increasing quality of care. In burn patients, the better data visibility was associated with a significant improvement in nutrient delivery.
Burns↗
Vitamins and trace elements: practical aspects of supplementation.
The role of micronutrients in parenteral nutrition include the following: (1) Whenever artificial nutrition is indicated, micronutrients, i.e., vitamins and trace elements, should be given from the first day of artificial nutritional support. (2) Testing blood levels of vitamins and trace elements in acutely ill patients is of very limited value. By using sensible clinical judgment, it is possible to manage patients with only a small amount of laboratory testing. (3) Patients with major burns or major trauma and those with acute renal failure who are on continuous renal replacement therapy or dialysis quickly develop acute deficits in some micronutrients, and immediate supplementation is essential. (4) Other groups at risk are cancer patients, but also pregnant women with hyperemesis and people with anorexia nervosa or other malnutrition or malabsorption states. (5) Clinicians need to treat severe deficits before they become clinical deficiencies. If a patient develops a micronutrient deficiency state while in care, then there has been a severe failure of care. (6) In the early acute phase of recovery from critical illness, where artificial nutrition is generally not indicated, there may still be a need to deliver micronutrients to specific categories of very sick patients. (7) Ideally, trace element preparations should provide a low-manganese product for all and a manganese-free product for certain patients with liver disease. (8) High losses through excretion should be minimized by infusing micronutrients slowly, over as long a period as possible. To avoid interactions, it would be ideal to infuse trace elements and vitamins separately: the trace elements over an initial 12-h period and the vitamins over the next 12-h period. (9) Multivitamin and trace element preparations suitable for most patients requiring parenteral nutrition are widely available, but individual patients may require additional supplements or smaller amounts of certain micronutrients, depending on their clinical condition.
Critical Illness↗
Update on clinical micronutrient supplementation studies in the critically ill.
PURPOSE OF REVIEW: During the past 2 years a number of studies, meta-analyses and reviews have shown that micronutrient supplementation may be beneficial in critical illness. Selenium is emerging as a particularly important micronutrient. This paper reviews the evidence from trials in the critically ill, putting mechanisms, methods and shortcomings into perspective. RECENT FINDINGS: There is growing evidence that antioxidant supplements, particularly high-dose selenium, may reduce mortality, infectious complications, and improve wound healing. Deleterious effects may result from prolonged high doses, whereas short-term high dose supplements are probably safe in most critically ill populations. SUMMARY: Plasma micronutrient concentrations are low during critical illness, as a result of losses, low intakes and dilution, and redistribution from plasma to tissues. An assessment of status is difficult. Micronutrient supplements appear beneficial in conditions such as major burns, trauma and sepsis and stroke, and are most likely to benefit patients with previous or actual depletion. The intravenous route seems more efficient than the enteral. Although chronic high intakes may be harmful, short-term interventions appear to be free of deleterious effects. Further research is required to determine the optimal micronutrient combinations and the doses required according to the timing of intervention and severity of disease.
Antioxidants↗
Is there really a survival benefit of SDD in burns?
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Anti-Bacterial Agents↗
Antioxidant micronutrients in major trauma and burns: evidence and practice.
There has been a growing interest in micronutrients as a result of their essential role in endogenous antioxidant defense mechanisms and immunity. Critically ill burn and trauma patients are characterized by an increased free radical production, which is proportional to the severity of the injury. In addition, they are at high risk of negative trace element balances, which contribute to the imbalance in endogenous antioxidant capacity and the extension of primary lesions. Although selenium, zinc, and vitamin C and E status are altered in all injured patients, patients with major burns are unique for having copper deficiency. In major burns, high-dose ascorbic acid for 24 hours achieves reduction of resuscitation fluid requirements by endothelial antioxidant mechanisms both in animal models and in 1 human trial. Supplementation trials in trauma and burns including selenium and zinc have shown that early provision of micronutrients improves recovery. Vitamin supplementation trials without selenium have not achieved definitive effects. The human studies show that reinforcing antioxidant defenses early in the course of major injury is rational and that substituting the large initial micronutrient losses of selenium and zinc is safe in trauma, as is the addition of copper in burns. The IV route seems the only way to deliver the doses required to obtain a clinical effect.
Antioxidants↗
Reduction of nosocomial pneumonia after major burns by trace element supplementation: aggregation of two randomised trials.
INTRODUCTION: Nosocomial pneumonia is a major source of morbidity and mortality after severe burns. Burned patients suffer trace element deficiencies and depressed antioxidant and immune defences. This study aimed at determining the effect of trace element supplementation on nosocomial or intensive care unit (ICU)-acquired pneumonia. METHODS: Two consecutive, randomised, double-blinded, supplementation studies including two homogeneous groups of 41 severely burned patients (20 placebo and 21 intervention) admitted to the burn centre of a university hospital were combined. Intervention consisted of intravenous trace element supplements (copper 2.5 to 3.1 mg/day, selenium 315 to 380 mug/day, and zinc 26.2 to 31.4 mg/day) for 8 to 21 days versus placebo. Endpoints were infections during the first 30 days (predefined criteria for pneumonia, bacteraemia, wound, urine, and other), wound healing, and length of ICU stay. Plasma and skin (study 2) concentrations of selenium and zinc were determined on days 3, 10, and 20. RESULTS: The patients, 42 +/- 15 years old, were burned on 46% +/- 19% of body surface: the combined characteristics of the patients did not differ between the groups. Plasma trace element concentrations and antioxidative capacity were significantly enhanced with normalisation of plasma selenium, zinc, and glutathione peroxidase concentrations in plasma and skin in the trace element-supplemented group. A significant reduction in number of infections was observed in the supplemented patients, which decreased from 3.5 +/- 1.2 to 2.0 +/- 1.0 episodes per patient in placebo group (p < 0.001). This was related to a reduction of nosocomial pneumonia, which occurred in 16 (80%) patients versus seven (33%) patients, respectively (p < 0.001), and of ventilator-associated pneumonia from 13 to six episodes, respectively (p = 0.023). CONCLUSION: Enhancing trace element status and antioxidant defences by selenium, zinc, and copper supplementation was associated with a decrease of nosocomial pneumonia in critically ill, severely burned patients.
Adult↗
[Thoracic surgery and underfeeding scientific evidences, diagnosis and treatment].
Underfeeding causes a significant increase of postoperative complications, particularly respiratory and infectious complications. Thoracic surgery is frequently required in patients suffering wasting diseases (cancer, COPD, cystic fibrosis), which increase the risk of malnutrition. The most important risk factors are preoperative hypoalbuminemia and BMI < 20. The deleterious effects of underfeeding may be corrected by a preoperative nutritional support for 7 to 15 days using oral supplements or enteral feeding: respiratory muscle strength is improved, immunity is restored, and overall complications are reduced. Therefore preoperative diagnosis of underfeeding is of utmost importance. In case of emergency surgery, the nutritional assessment on admission enables the introduction of early postoperative artificial feeding.
Humans↗
Enteral nutrition in critically ill patients with severe hemodynamic failure after cardiopulmonary bypass.
BACKGROUND & AIMS: The study was designed to investigate and quantify nutritional support, and particularly enteral nutrition (EN), in critically ill patients with severe hemodynamic failure. METHODS: Prospective, descriptive study in a surgical intensive care unit (ICU) in a university teaching hospital: patients aged 67+/-13 yrs (mean+/-SD) admitted after cardiac surgery with extracorporeal circulation, staying 5 days in the ICU with acute cardiovascular failure. Severity of disease was assessed with SAPS II, and SOFA scores. Variables were energy delivery and balance, nutrition route, vasopressor doses, and infectious complications. Artificial feeding delivered according to ICU protocol. EN was considered from day 2-3. Energy target was set 25 kcal/kg/day to be reached stepwise over 5 days. RESULTS: Seventy out of 1114 consecutive patients were studied, aged 67+/-17 years, and staying 10+/-7 days in the ICU. Median SAPS II was 43. Nine patients died (13%). All patients had circulatory failure: 18 patients required intra-aortic balloon-pump support (IABP). Norepinephrine was required in 58 patients (83%). Forty patients required artificial nutrition. Energy delivery was very variable. There was no abdominal complication related to EN. As a mean, 1360+/-620 kcal/kg/day could be delivered enterally during the first 2 weeks, corresponding to 70+/-35% of energy target. Enteral nutrient delivery was negatively influenced by increasing dopamine and norepinephrine doses, but not by the use of IABP. CONCLUSION: EN is possible in the majority of patients with severe hemodynamic failure, but usually results in hypocaloric feeding. EN should be considered in patients with careful abdominal and energy monitoring.
Aged↗
Can oxidative damage be treated nutritionally?
BACKGROUND & AIMS: Nutrition and dietary patterns have been shown to have direct impact on health of the population and of selected patient groups. The beneficial effects have been attributed to the reduction of oxidative damage caused by the normal or excessive free radical production. The papers aims at collecting evidence of successful supplementation strategies. METHODS: Review of the literature reporting on antioxidant supplementation trials in the general population and critically ill patients. RESULTS: Antioxidant vitamin and trace element intakes have been shown to be particularly important in the prevention of cancer, cardiovascular diseases, age related ocular diseases and in aging. In animal models, targeted interventions have been associated with reduction of tissue destruction is brain and myocardium ischemia-reperfusion models. In the critically ill antioxidant supplements have resulted in reduction of organ failure and of infectious complications. CONCLUSIONS: Antioxidant micronutrients have beneficial effects in defined models and pathologies, in the general population and in critical illness: ongoing research encourages this supportive therapeutic approach. Further research is required to determined the optimal micronutrient combinations and the doses required according to timing of intervention.
Animals↗
Negative impact of hypocaloric feeding and energy balance on clinical outcome in ICU patients.
BACKGROUND AND AIMS: Critically ill patients with complicated evolution are frequently hypermetabolic, catabolic, and at risk of underfeeding. The study aimed at assessing the relationship between energy balance and outcome in critically ill patients. METHODS: Prospective observational study conducted in consecutive patients staying > or = 5 days in the surgical ICU of a University hospital. Demographic data, time to feeding, route, energy delivery, and outcome were recorded. Energy balance was calculated as energy delivery minus target. Data in means+/-SD, linear regressions between energy balance and outcome variables. RESULTS: Forty eight patients aged 57+/-16 years were investigated; complete data are available in 669 days. Mechanical ventilation lasted 11+/-8 days, ICU stay 15+/-9 was days, and 30-days mortality was 38%. Time to feeding was 3.1+/-2.2 days. Enteral nutrition was the most frequent route with 433 days. Mean daily energy delivery was 1090+/-930 kcal. Combining enteral and parenteral nutrition achieved highest energy delivery. Cumulated energy balance was between -12,600+/-10,520 kcal, and correlated with complications (P < 0.001), already after 1 week. CONCLUSION: Negative energy balances were correlated with increasing number of complications, particularly infections. Energy debt appears as a promising tool for nutritional follow-up, which should be further tested. Delaying initiation of nutritional support exposes the patients to energy deficits that cannot be compensated later on.
Adolescent↗
Lactate and glucose metabolism in severe sepsis and cardiogenic shock.
OBJECTIVE: To evaluate the relative importance of increased lactate production as opposed to decreased utilization in hyperlactatemic patients, as well as their relation to glucose metabolism. DESIGN: Prospective observational study. SETTING: Surgical intensive care unit of a university hospital. PATIENTS: Seven patients with severe sepsis or septic shock, seven patients with cardiogenic shock, and seven healthy volunteers. INTERVENTIONS: C-labeled sodium lactate was infused at 10 micromol/kg/min and then at 20 micromol/kg/min over 120 mins each. H-labeled glucose was infused throughout. MEASUREMENTS AND MAIN RESULTS: Baseline arterial lactate was higher in septic (3.2 +/- 2.6) and cardiogenic shock patients (2.8 +/- 0.4) than in healthy volunteers (0.9 +/- 0.20 mmol/L, p < .05). Lactate clearance, computed using pharmacokinetic calculations, was similar in septic, cardiogenic shock, and controls, respectively: 10.8 +/- 5.4, 9.6 +/- 2.1, and 12.0 +/- 2.6 mL/kg/min. Endogenous lactate production was determined as the initial lactate concentration multiplied by lactate clearance. It was markedly enhanced in the patients (septic 26.2 +/- 10.5; cardiogenic shock 26.6 +/- 5.1) compared with controls (11.2 +/- 2.7 micromol/kg/min, p < .01). C-lactate oxidation (septic 54 +/- 25; cardiogenic shock 43 +/- 16; controls 65 +/- 15% of a lactate load of 10 micromol/kg/min) and transformation of C-lactate into C-glucose were not different (respectively, 15 +/- 15, 9 +/- 18, and 10 +/- 7%). Endogenous glucose production was markedly increased in the patients (septic 14.8 +/- 1.8; cardiogenic shock 15.0 +/- 1.5) compared with controls (7.2 +/- 1.1 micromol/kg/min, p < .01) and was not influenced by lactate infusion. CONCLUSIONS: In patients suffering from septic or cardiogenic shock, hyperlactatemia was mainly related to increased production, whereas lactate clearance was similar to healthy subjects. Increased lactate production was concomitant to hyperglycemia and increased glucose turnover, suggesting that the latter substantially influences lactate metabolism during critical illness.
Adult↗
An evaluation of the initial distribution volume of glucose to assess plasma volume during a fluid challenge.
UNLABELLED: Circulation blood volume can be estimated with the initial distribution volume of glucose (IDVG) method. In a prospective, observational study, we evaluated the effect of a fluid challenge on IDVG in individual patients. In 13 patients after cardiac surgery, IDVG was determined before and after the infusion of 7 mL/kg hydroxyethyl starch over 30 min. Eleven patients not requiring a fluid challenge served as control. IDVG was computed with a one-compartment exponential model, using plasma glucose concentrations at baseline and 3, 4, 5, 6, and 7 min after 5 g of glucose IV bolus. IDVG was repeated 3 times in the control group. IDVG did not change after a fluid challenge (85 +/- 14 versus 93 +/- 14 mL/kg, P = 0.08), and the power of the comparison was 0.25 for a P value of 0.05. The regression coefficient of the exponential fit of glucose versus time was 0.96 +/- 0.03 before, and 0.95 +/- 0.04 after starch infusion (not significant). In the control group, IDVG was 90 +/- 18 mL/kg, and the average individual coefficient of variation was 0.15 +/- 0.08. IDVG seems inadequate to assess individual response to fluid therapy. This limitation may be related to the weak reproducibility of IDVG. IMPLICATIONS: The initial distribution volume of glucose (IDVG) is supposed to reflect effective circulating blood volume. We assessed the sensitivity of this method to a fluid challenge in patients receiving a fluid challenge, and the reproducibility in otherwise stable patients. IDVG was not sensitive to a fluid challenge, and reproducibility was poor. Thus, clinical usefulness of IDVG seems limited.
Aged↗
Antioxidant nutrients: a systematic review of trace elements and vitamins in the critically ill patient.
OBJECTIVE: Critical illness is associated with the generation of oxygen free radicals and low endogenous antioxidant capacity leading to a condition of oxidative stress. We investigated whether supplementing critically ill patients with antioxidants, trace elements, and vitamins improves their survival. METHODS: We searched four bibliographic databases from 1980 to 2003 and included studies that were randomized, reported clinically important endpoints in critically ill patients, and compared various trace elements and vitamins to placebo. RESULTS: Eleven articles met the inclusion criteria. When the results of all the trials were aggregated, overall antioxidants were associated with a significant reduction in mortality [Risk Ratio (RR) 0.65, 95% confidence intervals (CI) 0.44-0.97, p=0.03] but had no effect on infectious complications. Studies that utilized a single trace element were associated with a significant reduction in mortality [RR 0.52, 95% CI 0.27-0.98, p=0.04] whereas combined antioxidants had no effect. Studies using parenteral antioxidants were associated with a significant reduction in mortality [RR 0.56, 95% CI 0.34-0,92, p=0.02] whereas studies of enteral antioxidants were not. Selenium supplementation (alone and in combination with other antioxidants) may be associated with a reduction in mortality [RR 0.59, 95% CI 0.32-1.08, p=0.09] while nonselenium antioxidants had no effect on mortality. CONCLUSIONS: Trace elements and vitamins that support antioxidant function, particularly high-dose parenteral selenium either alone or in combination with other antioxidants, are safe and may be associated with a reduction in mortality in critically ill patients.
Antioxidants↗
Effect of bicarbonate and lactate buffer on glucose and lactate metabolism during hemodiafiltration in patients with multiple organ failure.
OBJECTIVE: To compare the effects of sodium bicarbonate and lactate for continuous veno-venous hemodiafiltration (CVVHDF) in critically ill patients. DESIGN AND SETTINGS: Prospective crossed-over controlled trial in the surgical and medical ICUs of a university hospital. PATIENTS: Eight patients with multiple organ dysfunction syndrome (MODS) requiring CVVHDF. INTERVENTION: Each patient received the two buffers in a randomized sequence over two consecutive days. MEASUREMENTS AND RESULTS: The following variables were determined: acid-base parameters, lactate production and utilization ((13)C lactate infusion), glucose turnover (6,6(2)H(2)-glucose), gas exchange (indirect calorimetry). No side effect was observed during lactate administration. Baseline arterial acid-base variables were equal with the two buffers. Arterial lactate (2.9 versus 1.5 mmol/l), glycemia (+18%) and glucose turnover (+23%) were higher in the lactate period. Bicarbonate and glucose losses in CVVHDF were substantial, but not lactate elimination. Infusing (13)C lactate increased plasma lactate levels equally with the two buffers. Lactate clearance (7.8+/-0.8 vs 7.5+/-0.8 ml/kg per min in the bicarbonate and lactate periods) and endogenous production rates (14.0+/-2.6 vs 13.6+/-2.6 mmol/kg per min) were similar. (13)C lactate was used as a metabolic substrate, as shown by (13)CO(2) excretion. Glycemia and metabolic rate increased significantly and similarly during the two periods during lactate infusion. CONCLUSION: Lactate was rapidly cleared from the blood of critically ill patients without acute liver failure requiring CVVHDF, being transformed into glucose or oxidized. Lactate did not exert undesirable effects, except moderate hyperglycemia, and achieved comparable effects on acid-base balance to bicarbonate.
Acid-Base Equilibrium↗
Copper, selenium, zinc, and thiamine balances during continuous venovenous hemodiafiltration in critically ill patients.
BACKGROUND: Acute renal failure is a serious complication in critically ill patients and frequently requires renal replacement therapy, which alters trace element and vitamin metabolism. OBJECTIVE: The objective was to study trace element balances during continuous renal replacement therapy (CRRT) in intensive care patients. DESIGN: In a prospective randomized crossover trial, patients with acute renal failure received CRRT with either sodium bicarbonate (Bic) or sodium lactate (Lac) as a buffering agent over 2 consecutive 24-h periods. Copper, selenium, zinc, and thiamine were measured with highly sensitive analytic methods in plasma, replacement solutions, and effluent during 8-h periods. Balances were calculated as the difference between fluids administered and effluent losses and were compared with the recommended intakes (RI) from parenteral nutrition. RESULTS: Nineteen sessions were conducted in 11 patients aged 65 +/- 10 y. Baseline plasma concentrations of copper were normal, whereas those of selenium and zinc were below reference ranges; glutathione peroxidase was in the lower range of normal. The replacement solutions contained no detectable copper, 0.01 micromol Se/L (Bic and Lac), and 1.42 (Bic) and 0.85 (Lac) micromol Zn/L. Micronutrients were detectable in all effluents, and losses were stable in each patient; no significant differences were found between the Bic and Lac groups. The 24-h balances were negative for selenium (-0.97 micromol, or 2 times the daily RI), copper (-6.54 micromol, or 0.3 times the daily RI), and thiamine (-4.12 mg, or 1.5 times the RI) and modestly positive for zinc (20.7 micromol, or 0.2 times the RI). CONCLUSIONS: CRRT results in significant losses and negative balances of selenium, copper, and thiamine, which contribute to low plasma concentrations. Prolonged CRRT is likely to result in selenium and thiamine depletion despite supplementation at recommended amounts.
Acute Kidney Injury↗