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Background/Objective: Dysnatremia is common in severe traumatic brain injury (TBI) patients and may contribute to mortality. However, serum sodium variability has not been studied in TBI patients. We hypothesized that such variability would be independently associated with mortality. Methods: We collected 6-hourly serum sodium levels for the first 7 days of ICU admission from 240 severe TBI patients in 14 neurotrauma ICUs in Europe and Australia. We evaluated the association between daily serum sodium standard deviation (dNaSD), an index of variability, and 28-day mortality. Results: Patients were 46 ± 19 years of age with a median initial GCS of 6 [4–8]. Overall hospital mortality was 28%. Hypernatremia and hyponatremia occurred in 64% and 24% of patients, respectively. Over the first 7 days in ICU, serum sodium standard deviation was 2.8 [2.0–3.9] mmol/L. Maximum daily serum sodium standard deviation (dNaSD) occurred at a median of 2 [1–4] days after admission. There was a significant progressive decrease in dNaSD over the first 7 days (coefficient − 0.15 95% CI [− 0.18 to − 0.12], p < 0.001). After adjusting for baseline TBI severity, diabetes insipidus, the use of osmotherapy, the occurrence of hypernatremia, and hyponatremia and center, dNaSD was significantly independently associated with 28-day mortality (HR 1.27 95% CI (1.01–1.61), p = 0.048). Conclusions: Our study demonstrates that daily serum sodium variability is an independent predictor of 28-day mortality in severe TBI patients. Further prospective investigations are necessary to confirm the significance of sodium variability in larger cohorts of TBI patients and test whether attenuating such variability confers outcome benefits to such patients. [ABSTRACT FROM AUTHOR]

Purpose: We compared a restrictive fluid management strategy to usual care among critically ill patients with acute kidney injury (AKI) who had received initial fluid resuscitation.Methods: This multicenter feasibility trial randomized 100 AKI patients 1:1 in seven ICUs in Europe and Australia. Restrictive fluid management included targeting negative or neutral daily fluid balance by minimizing fluid input and/or enhancing urine output with diuretics administered at the discretion of the clinician. Fluid boluses were administered as clinically indicated. The primary endpoint was cumulative fluid balance 72 h from randomization.Results: Mean (SD) cumulative fluid balance at 72 h from randomization was - 1080 mL (2003 mL) in the restrictive fluid management arm and 61 mL (3131 mL) in the usual care arm, mean difference (95% CI) - 1148 mL (- 2200 to - 96) mL, P = 0.033. Median [IQR] duration of AKI was 2 [1-3] and 3 [2-7] days, respectively (median difference - 1.0 [- 3.0 to 0.0], P = 0.071). Altogether, 6 out of 46 (13%) patients in the restrictive fluid management arm and 15 out of 50 (30%) in the usual care arm received renal replacement therapy (RR 0.42; 95% CI 0.16-0.91), P = 0.043. Cumulative fluid balance at 24 h and 7 days was lower in the restrictive fluid management arm. The dose of diuretics was not different between the groups. Adverse events occurred more frequently in the usual care arm.Conclusions: In critically ill patients with AKI, a restrictive fluid management regimen resulted in lower cumulative fluid balance and less adverse events compared to usual care. Larger trials of this intervention are justified. [ABSTRACT FROM AUTHOR]

Background: Peri-operative coagulation management of patients receiving apixaban, a new oral anticoagulant, is difficult. The CytoSorb® hemoadsorption device might represent a therapeutic option to reduce apixaban's pharmacological and inflammatory effects during high-risk surgery. Case presentation: An 83-year-old woman treated with Apixaban underwent emergent redo mitral valve replacement for prosthetic valve endocarditis. A CytoSorb® cartridge was added to the cardio-pulmonary bypass (CPB) circuit. Apixaban-specific anti-factor Xa activity (AFXaA) were measured peri-operatively. After 100 minutes of CPB, a 50% AFXaA rate decrease was observed as compared to pre-CPB values. Furthermore, we noticed 39% and 44% reductions of AFXaA levels in comparison to the expected levels in patients with normal or altered renal function, respectively. Conclusion: Insertion of a CytoSorb® cartridge in the CPB was safe and associated with rapid correction of Apixaban-associated anticoagulation. [ABSTRACT FROM AUTHOR]

Inpatients are threatened by global malnutrition, but also by specific micronutrient (i.e., trace element and vitamins) deficiencies that frequently are overseen in the differential diagnosis of major organ dysfunctions. Some of them are related to specific geographic risks (iodine, iron, selenium, zinc, vitamin A), while others are pathology related, and finally many are associated with specific feeding patterns, including low dose enteral feeding. Among the pathologies in which laboratory blood investigations should include a micronutrient outwork, anemia is in the front line, followed by obesity with bariatric surgery, chronic liver disease, kidney disease, inflammatory bowel disease, cardiomyopathies and heart failure. The micronutrients at the highest risk are iron, zinc, thiamine, vitamin B12 and vitamin C. Admission to hospital has been linked with an additional risk of malnutrition—feeding below 1500 kcal/day was frequent and has been associated with a structural additional risk of insufficient micronutrient intake to cover basal needs. Although not evidence based, systematic administration of liberal thiamine doses upon admission, and daily complementation of inpatients' food and enteral feeding solutions with multi-micronutrient tablets might be considered. [ABSTRACT FROM AUTHOR]

Introduction: Regional citrate anticoagulation (RCA) is the recommended anticoagulation modality for continuous renal replacement therapy (CRRT). RCA was associated with a low rate of complications in randomized controlled trials. However, little is known about the type and rate of complications in real life. We sought to describe complications associated with RCA in comparison with those associated with heparin anticoagulation. Methods: In our institution, RCA has been the default anticoagulation modality for CRRT in all patients without contraindications since 2013. We have retrospectively reviewed all consecutive patients who received CRRT between January and December 2016 in our institution. For each CRRT session, we have assessed circuit duration, administered dose, as well as therapy-associated complications. Those parameters were compared according to whether the circuit was run in continuous veno-venous hemodialysis (CVVHD) mode with RCA or continuous veno-venous hemofiltration (CVVH) mode with heparin anticoagulation. Results: We analyzed 691 CRRT sessions in 121 patients. Of those 400 (57.9%) were performed in CVVHD-RCA mode and 291 (42.1%) in CVVH-Heparin Mode. Compared with -CVVH-Heparin mode, CVVHD-RCA mode was associated with a longer circuit lifespan (median duration 54.9 interquartile range [IQR 44.6] vs. 15.3 h [IQR 22.4], p < 0.0001). It was associated with a higher rate of metabolic acidosis 77 (20.2%) vs. 18 (7.2%), (p < 0.0001), alkalosis 186 (48.7%) vs. 43 (17.1%), (p= 0.0001), and hypocalcemia 96 (25.07%) vs. 26 events (10.79%), p < 0.0001. However, the majority of these alterations were of benign or moderate severity. Only one possible citrate intoxication was observed. Conclusions: CVVHD-RCA was associated with a much longer circuit life but an increased rate of minor metabolic complications, in particular acid-base derangements. Some of these complications might have been prevented by therapy adaptation. Medical and nursing staff education is of major importance in the implementation of an RCA protocol. [ABSTRACT FROM AUTHOR]

Background: Fluid accumulation frequently coexists with acute kidney injury (AKI) and is associated with increased risk for AKI progression and mortality. Among septic shock patients, restricted use of resuscitation fluid has been reported to reduce the risk of worsening of AKI. Restrictive fluid therapy, however, has not been studied in the setting of established AKI. Here, we present the protocol and statistical analysis plan of the REstricted fluid therapy VERsus Standard trEatment in Acute Kidney Injury-the REVERSE-AKI trial that compares a restrictive fluid therapy regimen to standard therapy in critically ill patients with AKI.Methods: REVERSE-AKI is an investigator-initiated, multinational, open-label, randomized, controlled, feasibility pilot trial conducted in seven ICUs in five countries. We aim to randomize 100 critically ill patients with AKI to a restrictive fluid treatment regimen vs standard management. In the restrictive fluid therapy regimen, the daily fluid balance target is neutral or negative. The primary outcome is the cumulative fluid balance assessed after 72 hours from randomization. Secondary outcomes include safety, feasibility, duration, and severity of AKI, and outcome at 90 days (mortality and dialysis dependence).Conclusions: This is the first multinational trial investigating the feasibility and safety of a restrictive fluid therapy regimen in critically ill patients with AKI.Trial Registration: clinical.trials.gov NCT03251131. [ABSTRACT FROM AUTHOR]

Patients with cardiogenic shock (CS) display systemic inflammation and a high rate of infections, suggesting important immune disturbances. To explore the immune response to CS, we prospectively measured, in 24 consecutive CS patients, differential white blood cell (WBC) counts and the cytokines IL-1β, IL-5, IL-6, IL-10, TNFα, IFNγ, MCP-1 and eotaxin (CCL11), at Day 1 (T1), day 3 (T2) and day 6-8 (T3). Secondary infections and their influence on cytokines and WBCs were determined. CS induced early (T1) neutrophilia and elevated levels of IL-6, IL-10 and MCP-1, correlating with shock severity. The eosinophil chemoattractant eotaxin was elevated at T1 and decreased thereafter, and a progressive rise of blood eosinophils was noted over time. Patients with the most severe shock had reduced lymphocytes and monocytes at T2 and T3. Sixty-two percent of patients developed an infection, which did not alter the profile of immune response, except from higher IL-6 levels at T2. Therefore, CS elicits an acute pro-inflammatory response, followed by a delayed increase in blood eosinophils, consistent with the development of a tissue repair response, as well as depletion of immune cells in the most severely affected patients, which might predispose to secondary infections. [ABSTRACT FROM AUTHOR]

Inpatients are threatened by global malnutrition, but also by specific micronutrient (i.e., trace element and vitamins) deficiencies that frequently are overseen in the differential diagnosis of major organ dysfunctions. Some of them are related to specific geographic risks (iodine, iron, selenium, zinc, vitamin A), while others are pathology related, and finally many are associated with specific feeding patterns, including low dose enteral feeding. Among the pathologies in which laboratory blood investigations should include a micronutrient outwork, anemia is in the front line, followed by obesity with bariatric surgery, chronic liver disease, kidney disease, inflammatory bowel disease, cardiomyopathies and heart failure. The micronutrients at the highest risk are iron, zinc, thiamine, vitamin B12 and vitamin C. Admission to hospital has been linked with an additional risk of malnutrition—feeding below 1500 kcal/day was frequent and has been associated with a structural additional risk of insufficient micronutrient intake to cover basal needs. Although not evidence based, systematic administration of liberal thiamine doses upon admission, and daily complementation of inpatients' food and enteral feeding solutions with multi-micronutrient tablets might be considered. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) and sepsis carry consensus definitions. The simultaneous presence of both identifies septic AKI. Septic AKI is the most common AKI syndrome in ICU and accounts for approximately half of all such AKI. Its pathophysiology remains poorly understood, but animal models and lack of histological changes suggest that, at least initially, septic AKI may be a functional phenomenon with combined microvascular shunting and tubular cell stress. The diagnosis remains based on clinical assessment and measurement of urinary output and serum creatinine. However, multiple biomarkers and especially cell cycle arrest biomarkers are gaining acceptance. Prevention of septic AKI remains based on the treatment of sepsis and on early resuscitation. Such resuscitation relies on the judicious use of both fluids and vasoactive drugs. In particular, there is strong evidence that starch-containing fluids are nephrotoxic and decrease renal function and suggestive evidence that chloride-rich fluid may also adversely affect renal function. Vasoactive drugs have variable effects on renal function in septic AKI. At this time, norepinephrine is the dominant agent, but vasopressin may also have a role. Despite supportive therapies, renal function may be temporarily or completely lost. In such patients, renal replacement therapy (RRT) becomes necessary. The optimal intensity of this therapy has been established, while the timing of when to commence RRT is now a focus of investigation. If sepsis resolves, the majority of patients recover renal function. Yet, even a single episode of septic AKI is associated with increased subsequent risk of chronic kidney disease. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is common in critically ill patients and associated with grim short- and long-term outcome. Although in the vast majority of cases AKI is multifactorial, with sepsis, shock and nephrotoxicity accounting for most episodes, specific causes of AKI are not uncommon. Despite remaining uncertainties regarding their prevalence in the ICU, prompt recognition of specific aetiologies of AKI is likely to ensure timely management, limit worsening of renal dysfunction, and ultimately limit renal and systemic consequences of AKI. The ability to recognize conditions that may be associated with specific aetiologies and the appropriate use of clinical imaging, biological and immunological tests, along with optimal assessment of the need for renal biopsies, should be part of routine ICU care. In this review, we summarize uncertainties, current knowledge and recent advances regarding specific types of AKI. We describe the most common specific causes as well as rare aetiologies requiring urgent management, and outline available tools that may be used during the diagnostic work-up along with their limitations. [ABSTRACT FROM AUTHOR]

Background: Omni ® (B. Braun, Germany) is a new-generation, continuous renal replacement therapy (CRRT) machine designed to improve user interface, minimize downtime and optimize renal dose delivery. It was never tested in humans. Methods: We used Omni ® to provide CRRT in 10 critically ill patients. We collected therapy data, metabolic parameters and evaluated user's satisfaction with a survey. Results: CRRT was delivered using Omni ® in CVVH-heparin (6 patients) and CVVHD-citrate (4 patients) modes for a total duration of 617.7 h. No adverse event was observed. The mean filter life was 22.8 (CVVH-heparin) and 33.5 (CVVHD-citrate) h. Alarms-related downtime corresponded to 5.9% of total therapy time. Delivered renal dose was 96.6% of prescribed. Satisfactory metabolic control and fluid removal were achieved. Overall, users evaluated interface, design and usability as excellent. Conclusion: CRRT in CVVH-heparin and CVVHD-citrate modes was provided using Omni ® in a safe and efficient way for 10 critically ill patients. [ABSTRACT FROM AUTHOR]

2012 saw the publication of four important trials investigating the choice of fluid therapy in patients suffering from critical illness or undergoing major surgery. These studies pave the way for more evidence-based administration of fluid in such patients. [ABSTRACT FROM AUTHOR]

Objectives: To assess the feasibility and satety ot a conservative approach to oxygen therapy in mechanically ventilated ICU patients. Design: Pilot prospective before-and-after study. Setting: A 22-bed multidisciplinary ICU of a tertiary care hospital in Australia. Patients: A total of 105 adult (18 years old or older) patients required mechanical ventilation for more than 48 hours: 51 patients during the "conventional" before period and 54 after a change to "conservative" oxygen therapy. Interventions: Implementation of a conservative approach to oxygen therapy (target Spo2 of 90-92%). Measurements and Main Results: We collected 3,169 datasets on 799 mechanical ventilation days. During conservative oxygen therapy the median time-weighted average Spo2 on mechanical ventilation was 95.5% (interquartile range, 94.0-97.3) versus 98.4% (973-99.1) (p< 0.001) during conventional therapy. The median Pao2 was 83 torr (71-94) versus 107 torr (94-131) (p < 0.001) with a change to a median Fio2 of 0.27 (0.24-0.30) versus 0.40 (0.35-0.44) (p < 0.001). Conservative oxygen therapy decreased the median total amount of oxygen delivered during mechanical ventilation by about two thirds (15,580 L [8,263-29,351 L] vs 5,1 22L [1,837-10,499 L]; p < 0.001). The evolution of the Pao2/Fio2 ratio was similar during the two periods, and there were no difference in any other biochemical or clinical outcomes. Conclusions: Conservative oxygen therapy in mechanically ventilated ICU patients was feasible and free of adverse biochemical, physiological, or clinical outcomes while allowing a marked decrease in excess oxygen exposure. Cur study supports the safety and feasibility of future pilot randomized controlled trials of conventional compared with conservative oxygen therapy. [ABSTRACT FROM AUTHOR]

Purpose: The choice of vascular access catheter may affect filter life during continuous renal replacement therapy (CRRT). In particular, differences in catheter design might affect the incidence of circuit clotting related to catheter malfunction. Design and setting: Sequential controlled study in a tertiary, adult intensive care unit (ICU). Aim: To compare circuit life when CRRT was performed with a Niagara™ catheter or a Medcomp™ catheter. Patients and measurements: We studied 46 patients with acute kidney injury requiring CRRT, all delivered with catheters in the femoral position. We obtained information on age, gender, disease severity score [acute physiology and chronic health evaluation (APACHE II) and APACHE III], filter life, heparin dose per hour, daily systemic hemoglobin concentration, platelet count, international normalized ratio (INR), and activated partial thromboplastin time (APTT) during CRRT. Results: We studied 254 circuits in 46 patients. Of these, 26 patients (140 circuits) used the Niagara catheter and 20 patients (114 circuits) used the Medcomp catheter. Median circuit life in the two groups were 11 h and 7.3 h, respectively ( p < 0.01). Patients using Medcomp catheters had a lower platelet count ( p = 0.04) and a lower hemoglobin concentration ( p = 0.01), but INR ( p = 0.16), APTT ( p = 0.46), anticoagulant treatment ( p = 0.89), and heparin dose per hour ( p = 0.24) were similar. After correcting for confounding variables by multivariable linear regression analysis, it was found that the choice of catheter is not an independent predictor of circuit life. On Kaplan-Meier survival analysis, circuit life was not significantly different between the two catheters ( p = 0.87). Conclusion: The choice of either the Niagara or Medcomp catheter does not appear to be a significant independent determinant of circuit life during CRRT. [ABSTRACT FROM AUTHOR]

Objective: To test the precision and limits of agreement of point-of-care testing (POCT)-based measurement of serum creatinine (Cr) in critically ill patients. Methods: We studied 250 paired blood samples from 82 critically ill patients from a general intensive care unit by simultaneous POCT and central laboratory testing (Jaffé method). Correlation, precision, bias, and limits of agreement were assessed. Possible confounders for interference of noncreatinine chromogens were evaluated by multivariate linear regression analysis. Results: The mean difference in serum Cr measured by central laboratory and POCT was ++9.6 μmol/L (95%% limits of agreement: −11.2 to ++30.4 μmol/L). The mean percentage difference between the two techniques was 8.7%% (95%% limits of agreement −7.8%% to ++25.1%%). On multivariate regression, the difference in serum Cr was increased with greater hemoglobin and lactate levels but decreased with greater bilirubin, albumin, and calcium levels. Conclusions: Compared with the central laboratory testing, POCT-based measurement of serum Cr in critically ill patients carried a small negative bias. This difference appeared affected by the blood levels of biochemical variables known to affect the Jaffé method. POCT-based Cr measurement appears sufficiently accurate for clinical use. [ABSTRACT FROM AUTHOR]