Felipe Dal Pizzol

Characteristics and outcomes of patients with cancer requiring admission to intensive care units: A prospective multicenter study*

Objective:To evaluate the characteristics and outcomes of patients with cancer admitted to several intensive care units. Knowledge on patients with cancer requiring intensive care is mostly restricted to single-center studies. Design:Prospective, multicenter, cohort study. Setting:Intensive care units from 28 hospitals in Brazil. Patients:A total of 717 consecutive patients included over a 2-mo period. Interventions:None. Measurements and Main Results:There were 667 (93%) patients with solid tumors and 50 (7%) patients had hematologic malignancies. The main reasons for intensive care unit admission were postoperative care (57%), sepsis (15%), and respiratory failure (10%). Overall hospital mortality rate was 30% and was higher in patients admitted because of medical complications (58%) than in emergency (37%) and scheduled (11%) surgical patients (p < .001). Adjusting for covariates other than the type of admission, the number of hospital days before intensive care unit admission (odds ratio [OR], 1.18; 95% confidence interval [CI], 1.01–1.37), higher Sequential Organ Failure Assessment scores (OR, 1.25; 95% CI, 1.17–1.34), poor performance status (OR, 3.40; 95% CI, 2.19 –5.26), the need for mechanical ventilation (OR, 2.42; 95% CI, 1.51–3.87), and active underlying malignancy in recurrence or progression (OR, 2.42; 95% CI, 1.51–3.87) were associated with increased hospital mortality in multivariate analysis. Conclusions:This large multicenter study reports encouraging survival rates for patients with cancer requiring intensive care. In these patients, mortality was mostly dependent on the severity of organ failures, performance status, and need for mechanical ventilation rather than cancer-related characteristics, such as the type of malignancy or the presence of neutropenia.

Validation of four prognostic scores in patients with cancer admitted to Brazilian intensive care units: results from a prospective multicenter study.

ObjectiveThe aim of the present study was to validate the Simplified Acute Physiology Score II (SAPS II) and 3 (SAPS 3), the Mortality Probability Models III (MPM0-III), and the Cancer Mortality Model (CMM) in patients with cancer admitted to several intensive care units (ICU).DesignProspective multicenter cohort study.SettingTwenty-eight ICUs in Brazil.PatientsSeven hundred and seventeen consecutive patients (solid tumors 93%; hematological malignancies 7%) included over a 2-month period.InterventionsNone.Measurements and main resultsDiscrimination was assessed by area under receiver operating characteristic (AROC) curves and calibration by Hosmer–Lemeshow goodness-of-fit test. The main reasons for ICU admission were postoperative care (57%), sepsis (15%) and respiratory failure (10%). The ICU and hospital mortality rates were 21 and 30%, respectively. When all 717 patients were evaluated, discrimination was superior for both SAPS II (AROCxa0=xa00.84) and SAPS 3 (AROCxa0=xa00.84) scores compared to CMM (AROCxa0=xa00.79) and MPM0-III (AROCxa0=xa00.71) scores (Pxa0<xa00.05 in all comparisons). Calibration was better using CMM and the customized equation of SAPS 3 score for South American countries (CSA). MPM0-III, SAPS II and standard SAPS 3 scores underestimated mortality (standardized mortality ratio, SMRxa0>xa01), while CMM tended to overestimation (SMRxa0=xa00.48). However, using the SAPS 3 for CSA resulted in more precise estimations of the probability of death [SMRxa0=xa01.02 (95% confidence intervalxa0=xa00.87–1.19)]. Similar results were observed when scheduled surgical patients were excluded.ConclusionsIn this multicenter study, the customized equation of SAPS 3 score for CSA was found to be accurate in predicting outcomes in cancer patients requiring ICU admission.

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

PURPOSEnDelirium 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.nnnMETHODSnAdult 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.nnnRESULTSnDuring 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.nnnCONCLUSIONnThe findings of our study suggest that the CAM-ICU is better predictor of outcome when compared with ICDSC.

Plasma Levels of Oxidative Stress Biomarkers and Long-Term Cognitive Performance after Severe Head Injury

1 Centro de Neurociências Aplicadas (CeNAp), Hospital Universitário, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil 2 Laboratório de Fisiopatologia Experimental, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil 3 Laboratório de Doenças Neurodegenerativas, Departamento de Farmacologia, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil 4 Serviço de Neurocirurgia, Hospital Governador Celso Ramos (HGCR), Florianópolis, SC, Brazil 5 Departamento de Cirurgia, Hospital Universitário, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil 6 Departamento de Clı́nica Médica, Hospital Universitário, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil

Effects of ketamine administration on mTOR and reticulum stress signaling pathways in the brain after the infusion of rapamycin into prefrontal cortex

Recent studies show that activation of the mTOR signaling pathway is required for the rapid antidepressant actions of glutamate N-methyl-D-aspartate (NMDA) receptor antagonists. A relationship between mTOR kinase and the endoplasmic reticulum (ER) stress pathway, also known as the unfolded protein response (UPR) has been shown. We evaluate the effects of ketamine administration on the mTOR signaling pathway and proteins of UPR in the prefrontal cortex (PFC), hippocampus, amygdala and nucleus accumbens, after the inhibiton of mTOR signaling in the PFC. Male adult Wistar rats received pharmacological mTOR inhibitor, rapamycin (0.2xa0nmol), or vehicle into the PFC and then a single dose of ketamine (15xa0mg/kg, i.p.). The immunocontent of mTOR, eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), eukaryotic elongation factor 2 kinase (eEF2K) homologous protein (CHOP), PKR-like ER kinase (PERK) and inositol-requiring enzyme 1 (IRE1) - alpha were determined in the brain. The mTOR levels were reduced in the rapamycin group treated with saline and ketamine in the PFC; p4EBP1 levels were reduced in the rapamycin group treated with ketamine in the PFC and nucleus accumbens; the levels of peEF2K were increased in the PFC in the vehicle group treated with ketamine and reduced in the rapamycin group treated with ketamine. The PERK and IRE1-alpha levels were decreased in the PFC in the rapamycin group treated with ketamine. Our results suggest that mTOR signaling inhibition by rapamycin could be involved, at least in part, with the mechanism of action of ketamine; and the ketamine antidepressant on ER stress pathway could be also mediated by mTOR signaling pathway in certain brain structures.

Efeito da transfusão de concentrado de hemácias sobre parâmetros de inflamação e estresse oxidativo em pacientes criticamente enfermos

INTRODUCTION: Red blood cell transfusions are common in intensive care units. For many years, transfusions of red blood were thought to have obvious clinical benefits. However, in recent years, the risks and benefits of blood transfusions have been examined more carefully, including the risk of increased morbidity and mortality due to transfusion-related immunomodulation effects. OBJECTIVES: To evaluate red blood cell transfusion effects and the relationship of this procedure to the production of inflammatory cytokines and oxidative damage in critically ill patients admitted to an intensive care unit. METHODS: For 6 months in 2008, we evaluated patients admitted to an intensive care unit who underwent packed red blood cell transfusions. Pre- and post-transfusion levels of interleukin-6, carbonylated proteins and thiobarbituric acid reactive substances were assessed. RESULTS: Serum post-transfusion interleukin-6 levels were reduced, and thiobarbituric acid reactive substances and carbonylated proteins were significantly increased. No statistically significant relationship was found between the levels of pre- and post-transfusion interleukin-6 and thiobarbituric acid reactive substances and the mortality rate. However, there was a significant relationship between levels of post-transfusion carbonylated proteins and mortality. CONCLUSION: Red blood cell transfusion is associated with increased oxidative damage markers and reduced interleukin-6 levels in critically ill patients.

Effects of omega-3 supplementation on interleukin and neurotrophin levels in an animal model of schizophrenia

New studies suggest that polyunsaturated fatty acids, such as omega-3, may reduce the symptoms of schizophrenia. The present study evaluated the preventive effect of omega-3 on interleukines (IL) and neurotrophin brain-derived neurotrophic factor (BDNF) levels in the brains of young rats subjected to a model of schizophrenia. Treatment was performed over 21 days, starting on the 30th day of rats life. After 14 days of treatment with omega-3 or vehicle, a concomitant treatment with saline or ketamine (25 mg/kg) was started and maintained until the last day of the experiment. BDNF levels in the rats prefrontal cortex were decreased at 1 h and 24 h after the last administration of ketamine, whereas the group administered with ketamine and omega-3 showed a decrease in BDNF levels only after 24 h. In contrast, both interventions induced similar responses in levels of IL-1β and IL6. These findings suggest that the similarity of IL-1β and IL6 levels in our experimental groups is due to the mechanism of action of ketamine on the immune system. More studies have to be carried out to explain this pathology. In conclusion, according to previous studies and considering the current study, we could suggest a prophylactic role of omega-3 against the outcome of symptoms associated with schizophrenia.

Role of hormonal levels on hospital mortality for male patients with severe traumatic brain injury

Abstract Introduction: Changes in hormone blood levels during the acute phase of traumatic brain injury (TBI) have been described in the literature. The objective was to investigate the association among several hormones plasma levels in the acute phase of severe TBI and the hospital mortality rate of male patients. Methods: The independent association among plasma levels of TSH, LH, FSH, GH, free T4, cortisol, IGF-1 and total testosterone was measured 10 hours and 30 hours after severe TBI and the hospital mortality of 60 consecutive male patients was evaluated. Results: At least one hormonal level abnormality was demonstrated in 3.6–73.1% of patients. The multiple logistic regressions showed a trend for an independent association among hospital mortality and normal or elevated LH levels measured at 10 hours (ORu2009=u20093.7, 95% CIu2009=u20090.8–16.3, pu2009=u20090.08) and 30 hours (ORu2009=u20093.9, 95% CIu2009=u20090.9–16.7, pu2009=u20090.06). Admission with abnormal pupils and a lower Glasgow Coma Score also were independently associated with hospital mortality. Conclusion: The hormonal changes are frequent in the acute phase of severe TBI. The hormones plasma levels, excepting the LH, are not highly consistent with the hospital mortality of male patients.

Mecanismos de disfunção da barreira hematoencefálica no paciente criticamente enfermo: ênfase no papel das metaloproteinases de matriz

This paper aims to describe the physiological basis of the blood-brain barrier components and its properties. Additionally, the particular effects of metalloproteinases and their control over the extracellular matrix and its relationship with blood-brain barrier dysfunction are discussed. Finally, the role of metalloproteinases on changes in the central nervous system in critically ill patients is discussed.