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The article presents the topics discussed in the 2011 issues. The early diagnosis of acute kidney injury remains as an issue with great importance, with an objective to establish early preventive measures in patients who are critically ill. Three epidemiologic studies have examined the results of postsurgical patients, revealed the presence of pre-existing morbidities including cirrhosis, respiratory or cardiac failure, and alcoholism.

Purpose: To confirm the pharmacodynamics and evaluate the efficacy of high-dose selenium (Se) administered by continuous infusion, following an initial loading bolus of selenite, on clinical outcome in critically ill patients with systemic inflammatory response syndrome (SIRS). Methods: Prospective, placebo-controlled, randomized, single-blinded phase II study in a multidisciplinary university hospital intensive care unit (ICU). Two groups of patients with SIRS, age >18 years, and Acute Physiology and Chronic Health Evaluation (APACHE) II ≥15 ( n = 35) were randomized to receive either placebo or intravenous selenite as a bolus-loading dose of 2,000 μg Se followed by continuous infusion of 1,600 μg Se per day for 10 days. Blood samples were analyzed before randomization (day 0) then at days 3, 7, and 10. Clinical outcome was assessed by Sequential Organ Failure Assessment (SOFA) score. Hospital-acquired pneumonia including ventilator-associated pneumonia (VAP), adverse events, and other safety parameters were monitored as secondary endpoints. Results: SOFA score decreased significantly in the selenite group at day 10 (1.3 ± 1.2 versus 4.6 ± 2.0, p = 0.0001). Early VAP rate was lower in the selenite group (6.7% versus 37.5%, p = 0.04), and hospital-acquired pneumonia was lower after ICU discharge ( p = 0.03). Glutathione peroxidase-3 (GPx-3) activity increased in both groups, reaching a maximum at day 7 (0.62 ± 0.24 versus 0.28 ± 0.14 U/mL, p = 0.001) in the selenite group. No adverse events attributable to selenite were observed. Conclusions: Daily infusion of 1,600 μg Se (as selenite), following an initial bolus of 2,000 μg, is novel and without short-term adverse events. High-dose parenteral selenite significantly increases Se status, improves illness severity, and lowers incidence of hospital-acquired pneumonia including early VAP for SIRS patients in ICU. [ABSTRACT FROM AUTHOR]

Purpose: The intravenous fluid 6% hydroxyethyl starch (130/0.4) (6% HES 130/0.4) is used widely for resuscitation but there is limited information on its efficacy and safety. A large-scale multi-centre randomised controlled trial (CHEST) in critically ill patients is currently underway comparing fluid resuscitation with 6% HES 130/0.4 to 0.9% sodium chloride on 90-day mortality and other clinically relevant outcomes including renal injury. This report describes the study protocol. Methods: CHEST will recruit 7,000 patients to concealed, random, parallel assignment of either 6% HES 130/0.4 or 0.9% sodium chloride for all fluid resuscitation needs whilst in the intensive care unit (ICU). The primary outcome will be all-cause mortality at 90 days post-randomisation. Secondary outcomes will include incident renal injury, other organ failures, ICU and hospital mortality, length of ICU stay, quality of life at 6 months, health economic analyses and in patients with traumatic brain injury, functional outcome. Subgroup analyses will be conducted in four predefined subgroups. All analyses will be conducted on an intention-to-treat basis. Results and conclusions: The study run-in phase has been completed and the main trial commenced in April 2010. CHEST should generate results that will inform and influence prescribing of this commonly used resuscitation fluid. [ABSTRACT FROM AUTHOR]

Objective: Systemic inflammatory response syndrome (SIRS) and sepsis remain the leading cause of death in the critically ill. A reduction in the antioxidant capacity, including selenoenzymes that are dependent on selenium (Se), could be a contributing factor. Se supplementation in septic patients have yielded conflicting results. We hypothesized that a high-dose Se supplementation would (1) improve markers of inflammation, nutrition and antioxidant defence, and (2) decrease mortality. Methods: This prospective, randomized, open-label, single-centre clinical trial included 150 patients with SIRS/sepsis and a SOFA score of >5. Patients in the Se+ group ( n = 75) received Se for 14 days (1,000 μg on day 1,500 μg/day on days 2-14). Patients in both the control (Se−) group ( n = 75) and the Se+ group received a standard Se dose (<75 μg/day). Plasma Se, whole-blood glutathione peroxidase (GPx) activity, C-reactive protein (CRP), procalcitonin (PCT), albumin, prealbumin and cholesterol levels, along with APACHE II and SOFA scores, were determined at baseline and on days 1-7 and day 14. Mortality was assessed at day 28. Results: Plasma Se and GPx activity were increased in the Se+ group from day 1 onwards. Negative correlations were demonstrated between plasma Se, CRP ( P = 0.035), PCT ( P = 0.022) and SOFA ( P = 0.001) at admission but not on days 7 or 14. Prealbumin and cholesterol increased in the Se+ group versus the respective baselines. Mortality was similar between groups, with no gender differences. Conclusion: High-dose Se substitution in patients with SIRS/sepsis increased plasma Se and GPx levels, but did not reduce mortality. Markers of inflammation were reduced similarly in both groups. [ABSTRACT FROM AUTHOR]

Acute renal failure on the intensive care unit is associated with significant mortality and morbidity. To determine recommendations for the prevention of acute kidney injury (AKI), focusing on the role of potential preventative maneuvers including volume expansion, diuretics, use of inotropes, vasopressors/vasodilators, hormonal interventions, nutrition, and extracorporeal techniques. A systematic search of the literature was performed for studies using these potential protective agents in adult patients at risk for acute renal failure/kidney injury between 1966 and 2009. The following clinical conditions were considered: major surgery, critical illness, sepsis, shock, and use of potentially nephrotoxic drugs and radiocontrast media. Where possible the following endpoints were extracted: creatinine clearance, glomerular filtration rate, increase in serum creatinine, urine output, and markers of tubular injury. Clinical endpoints included the need for renal replacement therapy, length of stay, and mortality. Studies are graded according to the international Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) group system Several measures are recommended, though none carries grade 1A. We recommend prompt resuscitation of the circulation with special attention to providing adequate hydration whilst avoiding high-molecular-weight hydroxy-ethyl starch (HES) preparations, maintaining adequate blood pressure using vasopressors in vasodilatory shock. We suggest using vasopressors in vasodilatory hypotension, specific vasodilators under strict hemodynamic control, sodium bicarbonate for emergency procedures administering contrast media, and periprocedural hemofiltration in severe chronic renal insufficiency undergoing coronary intervention. [ABSTRACT FROM AUTHOR]

Correcting hypovolemia is fundamental when treating the critically ill. Different hydroxyethylstarch (HES) preparations with different physicochemical characteristics (mean molecular weight (Mw), molar substitution (MS), C2/C6 ratio, balanced/unbalanced) are available. The possible detrimental effect of HES on kidney function has become a major objection to using HES. This review focuses on the effect of HES on kidney function. First and second-generation HES with high Mw (>200 kD) and high MS (>0.5) have been shown to impair kidney function in some studies of septic patients, especially when using hyperoncotic HES. More rapidly degradable HES preparations (Mw 130 kD; MS < 0.5) did not cause deterioration of kidney function in a variety of clinical conditions. Even when kidney function was impaired (serum creatinine >1.5 mg/dL) this HES preparation was without negative effect. Dissolving HES in a balanced solution instead of saline may further improve the safety of HES with regard to kidney function. Dose limitations of the specific HES preparation should be carefully considered. Hyperoncotic HES should not be used in patients who are at risk of developing kidney dysfunction. In patients without preexisting kidney dysfunction there seems to be no negative effects of modern HES preparations. In septic patients with reduced kidney function (serum creatinine >2.5 mg/dL) HES should be used cautiously, because studies of these patients are not available. Dissolving HES in a balanced solution further improves the safety of HES with regard to kidney function. At present, there seems to be no good reason to generally ban use of HES in our patients. [ABSTRACT FROM AUTHOR]

To describe the risk–benefit profile of hydroxyethyl starch (HES). Narrative review. (1) Efficacy: no single clinical study or systemic review has shown that administration of any HES solution confers a clinically relevant benefit compared to crystalloids in critically ill patients or surgical patients in need of volume replacement. Contrary to beliefs expecting a ratio of 4:1 or more for crystalloid to colloid volume need, recent studies of goal-directed resuscitation observed much lower ratios of between 1 and 1.6. (2) Safety: HES administration is associated with coagulopathy, nephrotoxicity, pruritus and increased long-term mortality. Clinical studies claiming that modern HES 130/0.4 is safe have serious methodological drawbacks and do not adequately address the safety concerns. Given the complete lack of superiority in clinical utility studies and the wide spectrum of severe side effects, the use of HES in the ICU should be stopped. The belief that four times as much crystalloid as colloid fluid volume is needed for successful resuscitation is being seriously questioned. [ABSTRACT FROM AUTHOR]

To confirm the influence of systemic inflammatory response syndrome (SIRS) on selenium (Se) levels and prospectively evaluate the relationship between serum Se concentration [Se], glutathione peroxidase activity [GPx-3] and injury severity in patients at the time of intensive care unit (ICU) admission. Prospective, observational study. Multidisciplinary University Hospital ICU. A total of 36 ICU patients and 23 healthy volunteer subjects (HVS). Healthy volunteer subjects were designated as controls (Group 1). ICU patients were divided into three groups: without SIRS (Group 2); with SIRS (Group 3); with SIRS and multiple organ dysfunction syndrome (MODS) (Group 4). The latter groups had APACHE II scores >15. [GPx-3] and [Se] were determined by standard methods within the first 48 h of admission to ICU. Kruskal–Wallis and Mann–Whitney U test were used for analysis of non-parametric continuous variables. The predictive value of [Se] and [GPx-3] for SIRS was calculated using a receiver operating characteristics (ROC) analysis. In SIRS and MODS patients [GPx-3] and [Se] decreased significantly ( P = 0.0001 and P = 0.002, respectively). After ICU admission [GPx-3] and [Se] had a predictive value for SIRS ([GPx-3] sensitivity: 90%, specificity: 86.2% (cut-off value: 0.5 U/mL); [Se]: sensitivity 90%, specificity 72.4% (cut-off value: 60 μg/L). [Se] had predictive value for ICU mortality ( P = 0.034). Systemic inflammatory response syndrome and MODS were associated with early decreases in [Se] and [GPx-3]. Low [Se] and [GPx-3] after ICU admission had a predictive value for SIRS, which may aid future selection of patients who could benefit from Se supplementation. [ABSTRACT FROM AUTHOR]

Crystalloids, artificial and natural colloids have been opposed as representing different strategies for shock resuscitation, but it may be relevant to distinguish fluids based on their oncotic characteristics. This study assessed the risk of renal adverse events in patients with shock resuscitated using hypooncotic colloids, artificial hyperoncotic colloids, hyperoncotic albumin or crystalloids, according to physician’s choice. International prospective cohort study including 1,013 ICU patients needing fluid resuscitation for shock. Patients suffering from cirrhosis or receiving plasma were excluded. Influence of different types of colloids and crystalloids on the occurrence of renal events (twofold increase in creatinine or need for dialysis) and mortality was assessed using multivariate analyses and propensity score. Statistical adjustment was based on severity at the time of resuscitation, risks factor for renal failure, and on variables influencing physicians’ preferences regarding fluids. A renal event occurred in 17% of patients. After adjustment on potential confounding factors and on propensity score for the use of hyperoncotic colloids, the use of artificial hyperoncotic colloids [OR: 2.48 (1.24–4.97)] and hyperoncotic albumin [OR: 5.99 (2.75–13.08)] was significantly associated with occurrence of renal event. Overall ICU mortality was 27.1%. The use of hyperoncotic albumin was associated with an increased risk of ICU death [OR: 2.79 (1.42–5.47)]. This study suggests that harmful effects on renal function and outcome of hyperoncotic colloids may exist. Although an improper usage of these compounds and confounding factors cannot be ruled out, their use should be regarded with caution, especially because suitable alternatives exist. [ABSTRACT FROM AUTHOR]

Objective: Cardiac surgery is an important risk factor for the development of acute renal failure. Cytosolic enzymes glutathione S-transferase (GST) A1 and P1 are present selectively in proximal and distal tubular cells, respectively. We determined the extent and site of tubular injury and examined if GST excretion may predict a clinically relevant change in renal function.Design and Setting: A prospective, observational study in 84 consecutive patients in the cardiac surgery intensive care unit of the University Medical Centre Nijmegen.Measurements and Results: Urinary GST enzyme excretion was determined 0-4 h and 20-24 h after cardiac surgery by enzyme-linked immunosorbent assay. Data are expressed as median and 5-95% range. Urinary excretion of GSTA1 was increased: 1.25 microg/mmol [0.31-10.20] creatinine at t =0-4 h ( p <0.0001, compared with controls; 0.25 [0.1-0.8]) and returned to normal values at t =20-24 h. Excretion of GSTP1 was 2.11 microg/mmol [0.52-17.82] creatinine ( p <0.0001) at t =0-4 h and remained significantly elevated: 0.84 [0.30-16.86] at t =20-24 h ( p =0.01) compared with controls (0.5 [0.2-1.1]). The ten patients with the highest urinary excretion of GSTA1 or GSTP1 did not demonstrate a different plasma creatinine level on postoperative day 3, compared with the ten patients with the lowest urinary excretion of GSTA1 or GSTP1.Conclusion: Uncomplicated cardiac surgery results in a statistically significant increase in the urinary excretion of GSTA1 and GSTP1 as compared with healthy controls, indicating proximal and distal tubular damage. However, this small increase in urinary excretion of GSTs is not associated with clinically relevant renal injury. [ABSTRACT FROM AUTHOR]

The article presents information regarding brain injury, hemodynamics, gastrointestinal tract, renal failure, metabolism, trauma, and postoperative. Considerable interest remains in measuring cerebral blood flow and in ascertaining the adequacy of cerebral blood flow, cerebral perfusion pressure, and substrate delivery/metabolism after acute brain injury. The combined technologies of magnetic resonance imaging, positron emission tomography, transcranial Doppler ultrasound, near infrared reflectance spectroscopy and cerebral microdialysis offer the prospect of better understanding the basic regulatory mechanisms that remain to be elucidated in neurophysiology.

The Editor-in-Chief has retracted this article [1] because a number of studies included in this review [2, 3, 4, 5, 6] (originally cited as references 18, 19, 20, 21, and 25) have subsequently been retracted. This has rendered the content of the review unreliable. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor about renal impairment in cardiac surgery patients receiving hydroxyethyl starch.