Cristiane Damiani Tomasi

Serum heat shock protein 70 levels, oxidant status, and mortality in sepsis

Animal studies as well as prospective randomized clinical trials associated sepsis with redox imbalance and oxidative stress, but other studies failed to establish a correlation between antioxidant-based therapies and improvement of sepsis condition. This is also true for studies on the role of the chaperone heat shock protein 70 (HSP70), which is increased in serum during sepsis. Heat shock protein 70 is affected at several levels by oxidative stress, but this relationship has never been studied in sepsis. Here, we evaluated the relationship between serum HSP70 immunocontent and oxidant status in sepsis. Patients with severe sepsis were followed up for 28 days after diagnosis, or until death. Up to a maximum of 12 h after sepsis diagnosis, serum was collected for determination of HSP70 immunocontent by Western blot and evaluation of oxidative parameters (TRAP [total radical-trapping antioxidant parameter], TBARSs [thiobarbituric acid-reactive substances], and carbonyl levels). Serum of sepsis patients presented enhanced HSP70 levels. Analysis of oxidative parameters revealed that septic patients with pronounced oxidative damage in serum had also increased HSP70 serum levels. Sepsis patients in whom serum oxidative stress markers were not different from control presented normal serum HSP70. Analysis of septic patients according to survival outcome also indicated that patients with increased HSP70 serum levels presented increased mortality. We concluded that serum HSP70 levels are modulated according to the patient oxidant status, and increased serum HSP70 is associated to mortality in sepsis.

Comparison of CAM-ICU and ICDSC for the detection of delirium in critically ill patients focusing on relevant clinical outcomes.

PURPOSE Delirium is a frequent and serious problem in the intensive care unit (ICU) that is associated with increased mortality, prolonged mechanical ventilation, and prolonged hospital length of stay (LOS). The main objective of the present study was to compare and assess the agreement between the diagnosis of delirium obtained by the Confusion Assessment Method for the ICU (CAM-ICU) and Intensive Care Delirium Screening Checklist (ICDSC) in patients admitted to the ICU and their association with outcomes. METHODS Adult patients admitted to the ICU for more than 24 hours between May and November 2008 were included. Patients with a Richmond Agitation-Sedation Scale score of -4 to -5 for more than 3 days were excluded. Delirium was evaluated twice a day by the ICDSC and CAM-ICU. Patients were followed-up until ICU discharge or for a maximum of 28 days. RESULTS During the study period, 383 patients were admitted to the ICU and 162 (42%) were evaluated; delirium was identified in 26.5% of patients by CAM-ICU and in 34.6% by ICDSC. There was agreement in diagnosing delirium diagnosis between the 2 methods in 42 (27.8%) patients and in excluding delirium in 105 (64.8%) patients. The ICDSC was positive in 14 (8.6%) patients in whom CAM-ICU was negative. Delirium, diagnosed either by ICDSC or CAM-ICU assessments, was associated with both significantly increased hospital LOS (14.8 ± 8.3 vs 9.8 ± 6.4, P < .001; 15.3 ± 8.7 vs 10.5 ± 7.1, P < .001, respectively), mortality in the ICU (11.1% vs 5.8%, P < .001; 12.5% vs 2.5%, P = .022), and in the hospital (10.7% vs 5.6%, P < .001; 23.2% vs 10.9%, P = .047). In addition, patients with positive ICDSC presenting with negative CAM-ICU had similar outcomes as compared with those without delirium. CONCLUSION The findings of our study suggest that the CAM-ICU is better predictor of outcome when compared with ICDSC.

Brain-derived neurotrophic factor and neuron-specific enolase, but not S100β, levels are associated to the occurrence of delirium in intensive care unit patients.

PURPOSE The aim of this study was to determine the association between serum concentrations of brain-derived neurotrophic factor (BDNF), neuron-specific enolase (NSE), and S100β and the occurrence of delirium in critically ill patients. MATERIAL AND METHODS This case-control study included 30 patients with delirium and 30 matched controls in a 16-bed general intensive care unit (ICU). Serum BDNF, NSE, and S100 concentrations were determined by enzyme-linked immunosorbent assay assays at the time of ICU admission and on the day before delirium was diagnosed. Delirium was diagnosed by confusion assessment method for the ICU. RESULTS At ICU admission, serum BDNF levels were significantly higher in delirious patients than in nondelirious controls (2.89 ± 1.48 vs 1.79 ± 0.89 ng/mL, respectively). When we compared serum S100 levels, there were no significant differences between the groups. Neuron-specific enolase values were significantly higher in the delirious patients than in the nondelirious controls (0.79 ± 0.03 ng/mL vs 0.59 ± 0.01 ng/mL, respectively). When patients who earlier developed delirium were separately analyzed, it was determined that serum NSE and BDNF levels at admission were significant higher only in this group. CONCLUSIONS Our results suggest that admission serum BDNF and NSE levels are associated with the occurrence of delirium in ICU patients.

The validity and reliability of the portuguese versions of three tools used to diagnose delirium in critically ill patients

OBJECTIVES: The objectives of this study are to compare the sensitivity and specificity of three diagnostic tools for delirium (the Intensive Care Delirium Screening Checklist, the Confusion Assessment Method for Intensive Care Units and the Confusion Assessment Method for Intensive Care Units Flowsheet) in a mixed population of critically ill patients, and to validate the Brazilian Portuguese Confusion Assessment Method for Intensive Care Units. METHODS: The study was conducted in four intensive care units in Brazil. Patients were screened for delirium by a psychiatrist or neurologist using the Diagnostic and Statistical Manual of Mental Disorders. Patients were subsequently screened by an intensivist using Portuguese translations of the three tools. RESULTS: One hundred and nineteen patients were evaluated and 38.6% were diagnosed with delirium by the reference rater. The Confusion Assessment Method for Intensive Care Units had a sensitivity of 72.5% and a specificity of 96.2%; the Confusion Assessment Method for Intensive Care Units Flowsheet had a sensitivity of 72.5% and a specificity of 96.2%; the Intensive Care Delirium Screening Checklist had a sensitivity of 96.0% and a specificity of 72.4%. There was strong agreement between the Confusion Assessment Method for Intensive Care Units and the Confusion Assessment Method for Intensive Care Units Flowsheet (kappa coefficient = 0.96). CONCLUSION: All three instruments are effective diagnostic tools in critically ill intensive care unit patients. In addition, the Brazilian Portuguese version of the Confusion Assessment Method for Intensive Care Units is a valid and reliable instrument for the assessment of delirium among critically ill patients.

Sodium butyrate decreases the activation of NF-κB reducing inflammation and oxidative damage in the kidney of rats subjected to contrast-induced nephropathy

BACKGROUND Contrast-induced nephropathy (CIN) is associated with a combination of hypoxic and toxic renal tubular damage, renal endothelial dysfunction and altered intra-renal microcirculation. Recently, sodium butyrate (SB) has been focused on since it possesses anti-inflammatory activities. Thus, based on the lack of information on the effects of SB in acute kidney injury (AKI), we investigated the possible effects of SB after CIN in rats. METHODS Wistar rats were divided into three groups: (1 sham) control, (2 MI) AKI treated with contrast medium and (3 MI + SB) AKI plus SB. Six days after contrast administration, blood and kidney were removed for the determination of creatinine, interleukin (IL)-6 levels, oxidative damage parameters and histologic analyses. Nuclear factor kappa B (NF-κB), pIκBα and vasodilator-stimulated phosphoprotein (VASP) protein content were determined by immunoblotting. RESULTS After 6 days, the levels of creatinine increased significantly in the MI group, and this was attenuated using SB. SB treatment was associated with a decrease on the levels of lipid peroxidation, but not the protein oxidation, and IL-6 levels, as well as tubular damage. These effects are probably mediated, in part, by a decrease on the activation of NF-κB in the kidney, but not alteration in pVASP content. CONCLUSIONS The current experiment suggests that NF-κB induced an inflammatory response after CIN and SB could inhibit NF-κB expression protecting against CIN in rats.

Hypomagnesemia as a risk factor for the non-recovery of the renal function in critically ill patients with acute kidney injury

BACKGROUND The aim of this study was to evaluate the role of hypomagnesemia as a risk factor for the development of acute kidney injury (AKI) and non-recovery of renal function in critically ill patients. METHODS A cohort study was conducted by collecting data from March to June 2011 in 232 patients who were admitted into an intensive care unit (ICU). Magnesium serum levels were measured daily during ICU stay. Hypomagnesemia was defined as an episode of serum magnesium concentration of <0.70 mmol/L during ICU stay. The Risk, Injury, Failure, Loss and End-stage kidney disease (RIFLE) criteria were used to define AKI. Renal function recovery was defined as an absence of AKI by the RIFLE criteria over a 48-h period, or at ICU discharge, in the patients who developed AKI during ICU stay. RESULTS The presence of hypomagnesemia was similar in patients with or without AKI (47 and 62%, respectively, P = 0.36). The presence of hypomagnesemia was higher in patients who did not recover renal function when compared with patients who recovered renal function (70 versus 31%, P = 0.003). A multivariate analysis identified hypomagnesemia as an independent risk factor for non-recovery of renal function (P = 0.005). Patients with and without hypomagnesemia had similar mortality rates (P = 0.63). CONCLUSIONS Hypomagnesemia was an independent risk factor for non-recovery of renal function in a cohort of critically ill AKI patients.

The Effects of N-Acetylcysteine and Deferoxamine on Plasma Cytokine and Oxidative Damage Parameters in Critically Ill Patients With Prolonged Hypotension: A Randomized Controlled Trial

Reactive oxygen species and inflammation have been implicated in renal tubule cell injury. However, there is some controversy concerning whether antioxidants might attenuate oxidative damage and inflammation in humans after hypotension in the setting of critical illness. This study was a prospective, randomized, double‐blinded, placebo‐controlled study that included patients with hypotension. Patients were randomized to receive either N‐acetylcysteine (NAC; 50 mg/kg by 4 hours followed by 100 mg/kg/d for 48 hours diluted in 5% glucose) and deferoxamine (DFX; at a single dose of 1000 mg diluted in 5% glucose) or placebo. The primary study outcome was the serum levels of markers of oxidative damage and inflammatory response. Secondary outcomes included the incidence of acute renal failure, serum creatinine at hospital discharge, intensive care unit length of stay, and length of hospital stay. Thirty patients were enrolled in the study. The use of NAC plus DFX decreased the oxidative damage parameters but not plasma interleukin‐6 levels. In contrast, plasma nitrite levels increased 24 hours after NAC plus DFX administration. On analysis of secondary outcomes, it was observed that creatinine levels at hospital discharge were lower in patients receiving NAC plus DFX when compared with placebo. NAC plus DFX administration was able to decrease plasma markers of oxidative damage and creatinine levels at hospital discharge.

Septic encephalopathy: does inflammation drive the brain crazy?

Sepsis and the multiorgan dysfunction syndrome are among the most common reasons for admission to an intensive care unit, and are a leading cause of death. During sepsis, the central nervous system (CNS) is one of the first organs affected, and this is clinically manifested as sepsis-associated encephalopathy (SAE). It is postulated that the common final pathway that leads to SAE symptoms is the deregulation of neurotransmitters, mainly acetylcholine. Thus, it is supposed that inflammation can affect neurotransmitters, which is associated with SAE development. In this review, we will cover the current evidence (or lack thereof) for the mechanisms by which systemic inflammation interferes with the metabolism of major CNS neurotransmitters, trying to explain how systemic inflammation drives the brain crazy.

CAM-ICU and ICDSC Agreement in Medical and Surgical ICU Patients Is Influenced by Disease Severity

Introduction Delirium is a prevalent condition in patients admitted to intensive care units (ICU) associated with worse outcomes. The principal aim of the present study was compare the agreement between two tools for delirium assessment in medical and surgical patients admitted to the ICU. Methods Consecutive adult surgical and medical patients admitted to the ICU for more than 24 hours between March 2009 and September 2010 were included. Delirium was evaluated twice a day using the Intensive Care Delirium Screening Checklist (ICDSC) and Confusion Assessment Method adapted to the Intensive Care Unit (CAM-ICU). The kappa (k) and AC1 coefficients were calculated as a measure of agreement between the CAM-ICU and ICDSC. Results A total of 595 patients were enrolled in the study. There were 69 (12%) emergency surgical, 207 (35%) elective surgical and 319 (54%) medical patients. Delirium incidence evaluated by the ICDSC, but not by the CAM-ICU, was similar among the three groups. Overall agreement between CAM-ICU and ICDSC was moderate (k = 0.5) to substantial (AC1 = 0.71). In medical patients the agreement between the two instruments was moderate (k = 0.53) to substantial (AC1 = 0.76). The agreement between the two tools in emergency surgical patients was also moderate (k = 0.53) to substantial (AC1 = 0.68). In elective surgical patients the agreement between the two instruments was low (k = 0.42) to substantial (AC1 = 0.74).Agreement rates seemed to be influenced by disease severity. The agreement rate in the general ICU population with APACHE II = <14 was k = 0.57 and AC1 = 0.81, compared to k = 0.44 and AC1 = 0.59, in patients with more severe disease. This was even more different when the need for mechanical ventilation was used as a surrogate of disease severity. Conclusions The agreement rates between CAM-ICU and ICDSC may vary between different groups of ICU patients and seems to be affected by disease severity.

Incidência de delirium durante a internação em unidade de terapia intensiva em pacientes pré-tratados com estatinas no pós-operatório de cirurgia cardíaca

OBJECTIVE To determine the association between the preoperative administration of statins and postoperative delirium in a prospective cohort of patients undergoing cardiac surgery. METHODS All adult patients who were admitted to the intensive care unit following cardiac surgery between January and June 2011 were included. Delirium was screened during the postoperative period using the Confusion Assessment Method for Intensive Care Unit (CAM-ICU) and Intensive Care Delirium Screening Checklist (ICDSC). RESULTS A total of 169 patients underwent elective cardiac surgery, and 40.2% of the patients were treated preoperatively with statins. Delirium was identified using the CAM-ICU in 14.9% of patients not taking preoperative statins in comparison with 11.8% of the patients taking statins (p = 0.817). Using the ICDSC, delirium was identified in 18.8% of patients not taking statins in comparison with 10.3% of the patients taking statins (p = 0.191). CONCLUSION The use of preoperative statins is not correlated with postoperative delirium in patients undergoing cardiac surgery.