[show abstract][hide abstract] ABSTRACT: To determine the relationship between enteral nutrition discontinuation and outcome in general critically ill patients.
All patients admitted to a mixed intensive care unit in a tertiary care hospital from May-August 2009 were screened for an indication for enteral nutrition. Patients were followed up until leaving the intensive care unit or a maximum of 28 days. The gastrointestinal failure score was calculated daily by adding values of 0 if the enteral nutrition received was identical to the nutrition prescribed, 1 if the enteral nutrition received was at least 75% of that prescribed, 2 if the enteral nutrition received was between 50-75% of that prescribed, 3 if the enteral nutrition received was between 50-25% of that prescribed, and 4 if the enteral nutrition received was less than 25% of that prescribed.
The mean, worst, and categorical gastrointestinal failure scores were associated with lower survival in these patients. Age, categorical gastrointestinal failure score, type of admission, need for mechanical ventilation, sequential organ failure assessment, and Acute Physiologic and Chronic Health Evaluation II scores were selected for analysis with binary regression. In both models, the categorical gastrointestinal failure score was related to mortality.
The determination of the difference between prescribed and received enteral nutrition seemed to be a useful prognostic marker and is feasible to be incorporated into a gastrointestinal failure score.
Clinics (São Paulo, Brazil) 01/2013; 68(2):173-8. · 1.59 Impact Factor
[show abstract][hide abstract] ABSTRACT: INTRODUCTION: Because of its relevance to the functioning of the central nervous system, brain-derived neurotrophic factor (BDNF) has been implicated in the pathogenesis of different neuropsychiatric diseases. Whether the BDNF level can be a marker of brain dysfunction and thus predict mortality in critically ill patients is not known. Thus we aimed to determine whether the plasma levels of BDNF are associated with morbidity and mortality in critically ill patients. METHODS: Healthy volunteers (n = 40) and consecutive patients older than 18 years (n = 76) admitted for more than 24 hours in an Intensive Care Unit (ICU) in a University hospital between July and October 2010 were included in the present study. First blood samples were collected within 12 hours of enrollment (D0), and a second sample, 48 hours after (D2) for determination of plasma BDNF levels. The relation between BDNF levels and mortality was the primary outcome. The secondary outcomes were the relation between BDNF levels and delirium and coma-free days (DCFD) and ICU and hospital length of stay (LOS). RESULTS: Admission plasma levels of BDNF were higher in ICU patients when compared with healthy volunteers (1,536 (962) versus 6,565 (2,838) pg/ml). The mean BDNF D2 was significantly lower in nonsurvivor patients (5,865 (2,662) versus 6,741 (2,356) pg/ml). After adjusting for covariates, BDNF levels, the need for mechanical ventilation, and sepsis were associated with mortality. Even in patients without clinically detectable brain dysfunction, lower BDNF D2 levels were associated with mortality. BDNF D2 had a mild correlation to DCFD (r = 0.44), but not to ICU and hospital LOS. In addition, plasma BDNF did not correlate to different plasma cytokines and platelets levels. CONCLUSIONS: The plasma levels of BDNF were independently associated with mortality, even in the absence of clinically detectable brain dysfunction.
Critical care (London, England) 12/2012; 16(6):R234. · 4.72 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.MethodsA 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.ResultsThe 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.
[show abstract][hide abstract] ABSTRACT: In sepsis, TLR-4 modulates the migration of neutrophils to infectious foci, favoring bacteremia and mortality. In experimental sepsis organ dysfunction and cytokines released by activated macrophages can be reduced by gastrin-releasing peptide receptor (GRPR) antagonist, RC-3095. Here we report a link between GRPR and TLR-4 in experimental models and in sepsis patients. RAW 264.7 culture cells were exposed to LPS or TNF-α and, RC-3095 (10ng/ml). Male Wistar rats were subjected to CLP and RC-3095 was administered (3 mg/kg, subcutaneously); after 6 hours we removed the blood, bronchoalveolar lavage, peritoneal lavage and lung. Human patients with a clinical diagnosis of sepsis received a continuous infusion with RC-3095 (3 mg/kg, intravenous) over a period of 12 h and plasma was collected before and after RC-3095 administration and, in a different set of patients with SIRS or sepsis, GRP plasma levels were determined. RC-3095 inhibited TLR-4, ERK1/2, JNK, and Akt, decreased activation of AP-1, NF-kB and IL-6 in macrophages stimulated by LPS. It also decreased IL-6 release from macrophages stimulated by TNF-α. RC-3095 treatment in CLP rats decreased lung TLR-4, reduced the migration of cells to the lung, reduced systemic cytokines, and bacterial dissemination. Patients with sepsis and systemic inflammatory response syndrome have elevated plasma levels of GRP, which associates with clinical outcome in the sepsis patients. These findings highlight the role of GRPR signaling in sepsis outcome and the beneficial action of GRPR antagonists in controlling the inflammatory response in sepsis through a mechanism involving, at least, inhibition of TLR-4 signaling.
[show abstract][hide abstract] ABSTRACT: To determine the association between the preoperative administration of statins and postoperative delirium in a prospective cohort of patients undergoing cardiac surgery.
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).
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).
The use of preoperative statins is not correlated with postoperative delirium in patients undergoing cardiac surgery.
Revista brasileira de terapia intensiva. 03/2012; 24(1):52-57.
[show abstract][hide abstract] ABSTRACT: 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.
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.
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.
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.
[show abstract][hide abstract] ABSTRACT: 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.
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.
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.
The agreement rates between CAM-ICU and ICDSC may vary between different groups of ICU patients and seems to be affected by disease severity.
PLoS ONE 01/2012; 7(11):e51010. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
The Journal of Clinical Pharmacology 11/2011; 52(9):1365-72. · 2.84 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
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.
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.
The findings of our study suggest that the CAM-ICU is better predictor of outcome when compared with ICDSC.
Journal of critical care 07/2011; 27(2):212-7. · 2.13 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
[show abstract][hide abstract] ABSTRACT: 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.
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.
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)
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.
Clinics (São Paulo, Brazil) 01/2011; 66(11):1917-22. · 1.59 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
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.
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.
Our results suggest that admission serum BDNF and NSE levels are associated with the occurrence of delirium in ICU patients.
Journal of critical care 11/2010; 26(2):133-7. · 2.13 Impact Factor
[show abstract][hide abstract] ABSTRACT: Objective: To evaluate the relationship between brain damage biomarkers and mortality in the intensive care unit (ICU). Methods: The sample comprised 70 patients admitted to an ICU. Blood samples were collected from all patients on ICU admission, and levels of S100β and neuron-specific enolase (NSE) were determined by ELISA. Results: Acute Physiologic and Chronic Health Evaluation (APACHE II) score was associated with mortality, but NSE and S100β were not associated with this outcome. In contrast, S100β levels were significantly higher in delirious and non-delirious patients who required mechanical ventilation during ICU stay. Conclusion: Levels of brain biomarkers at the time of ICU admission did not predict mortality in critically ill patients.
Revista Brasileira de Psiquiatria 35(3):267-70. · 1.86 Impact Factor