Fernando Godinho Zampieri

C-Reactive Protein/Albumin Ratio Predicts 90-Day Mortality of Septic Patients

Introduction Residual inflammation at ICU discharge may have impact upon long-term mortality. However, the significance of ongoing inflammation on mortality after ICU discharge is poorly described. C-reactive protein (CRP) and albumin are measured frequently in the ICU and exhibit opposing patterns during inflammation. Since infection is a potent trigger of inflammation, we hypothesized that CRP levels at discharge would correlate with long-term mortality in septic patients and that the CRP/albumin ratio would be a better marker of prognosis than CRP alone. Methods We evaluated 334 patients admitted to the ICU as a result of severe sepsis or septic shock who were discharged alive after a minimum of 72 hours in the ICU. We evaluated the performance of both CRP and CRP/albumin to predict mortality at 90 days after ICU discharge. Two multivariate logistic models were generated based on measurements at discharge: one model included CRP (Model-CRP), and the other included the CRP/albumin ratio (Model-CRP/albumin). Results There were 229 (67%) and 111 (33%) patients with severe sepsis and septic shock, respectively. During the 90 days of follow-up, 73 (22%) patients died. CRP/albumin ratios at admission and at discharge were associated with a poor outcome and showed greater accuracy than CRP alone at these time points (p = 0.0455 and p = 0.0438, respectively). CRP levels and the CRP/albumin ratio were independent predictors of mortality at 90 days (Model-CRP: adjusted OR 2.34, 95% CI 1.14–4.83, p = 0.021; Model-CRP/albumin: adjusted OR 2.18, 95% CI 1.10–4.67, p = 0.035). Both models showed similar accuracy (p = 0.2483). However, Model-CRP was not calibrated. Conclusions Residual inflammation at ICU discharge assessed using the CRP/albumin ratio is an independent risk factor for mortality at 90 days in septic patients. The use of the CRP/albumin ratio as a long-term marker of prognosis provides more consistent results than standard CRP values alone.

Sepsis-associated encephalopathy: not just delirium

Sepsis is a major cause of mortality and morbidity in intensive care units. Organ dysfunction is triggered by inflammatory insults and tissue hypoperfusion. The brain plays a pivotal role in sepsis, acting as both a mediator of the immune response and a target for the pathologic process. The measurement of brain dysfunction is difficult because there are no specific biomarkers of neuronal injury, and bedside evaluation of cognitive performance is difficult in an intensive care unit. Although sepsis-associated encephalopathy was described decades ago, it has only recently been subjected to scientific scrutiny and is not yet completely understood. The pathophysiology of sepsis-associated encephalopathy involves direct cellular damage to the brain, mitochondrial and endothelial dysfunction and disturbances in neurotransmission. This review describes the most recent findings in the pathophysiology, diagnosis, and management of sepsis-associated encephalopathy and focuses on its many presentations.

Extracorporeal membrane oxygenation for severe respiratory failure in adult patients: A systematic review and meta-analysis of current evidence

BACKGROUND Extracorporeal membrane oxygenation (ECMO) for acute respiratory failure is still a matter of debate. METHODS We performed a structured search on Pubmed, EMBASE, Lilacs, and the Cochrane Library for randomized controlled trials and observational case-control studies with severity-paired patients, evaluating the use of ECMO on severe acute respiratory failure in adult patients. A random-effect model using DerSimonian and Laird method for variance estimator was performed to evaluate the effect of ECMO use on hospital mortality. Heterogeneity between studies was assessed with Cochrans Q statistic and Higgins I(2). RESULTS Three studies were included on the metanalysis, comprising 353 patients in the main analysis, in which 179 patients were ECMO supported. One study was a randomized controlled trial and two were observational studies with a propensity score matching. The most common reason for acute respiratory failure was influenza H1N1 pneumonia (45%) and pneumonia (33%). ECMO was not associated with a reduction in hospital mortality (OR = 0.71; CI 95% = 0.34 - 1.47; P = 0.358). If alternative severity-pairing method presented by the two observational studies was included, a total of 478 cases were included, in which 228 received ECMO support. In the former analysis, ECMO had a benefit on hospital mortality (OR = 0.52; CI 95% = 0.35 - 0.76; P < 0.001). CONCLUSION Extracorporeal membrane oxygenation benefit on hospital mortality is unclear. Results were sensitive to statistical analysis, and no definitive conclusion can be drawn from the available data. More studies are needed before the widespread use of ECMO can be recommended.

Failure to reduce C-reactive protein levels more than 25% in the last 24 hours before intensive care unit discharge predicts higher in-hospital mortality: A cohort study ☆,☆☆

PURPOSE To discharge a patient from the intensive care unit (ICU) is a complex decision-making process because in-hospital mortality after critical illness may be as high as up to 27%. Static C-reactive protein (CRP) values have been previously evaluated as a predictor of post-ICU mortality with conflicting results. Therefore, we evaluated the CRP ratio in the last 24 hours before ICU discharge as a predictor of in-hospital outcomes. METHODS A retrospective cohort study was performed in 409 patients from a 6-bed ICU of a university hospital. Data were prospectively collected during a 4-year period. Only patients discharged alive from the ICU with at least 72 hours of ICU length of stay were evaluated. RESULTS In-hospital mortality was 18.3% (75/409). Patients with reduction less than 25% in CRP concentrations at 24 hours as compared with 48 hours before ICU discharge had a worse prognosis, with increased mortality (23% vs 11%, P = .002) and post-ICU length of stay (26 [7-43] vs 11 [5-27] days, P = .036). Moreover, among hospital survivors (n = 334), patients with CRP reduction less than 25% were discharged later (hazard ratio, 0.750; 95% confidence interval, 0.602-0.935; P = .011). CONCLUSIONS In this large cohort of critically ill patients, failure to reduce CRP values more than 25% in the last 24 hours of ICU stay is a strong predictor of worse in-hospital outcomes.

Cathelicidin LL-37 bloodstream surveillance is down regulated during septic shock

Host defense peptides are ancient weapons of the innate immunity. The human cathelicidin LL-37 protects the epithelial barrier against infection and is constitutively secreted in the bloodstream by immune cells. Current knowledge claims that LL-37 is up regulated upon infection. LL-37 can protect against bacterial infections and possesses many immunomodulatory properties. Here, we show that the human host defense peptide LL-37 is down regulated during septic shock. Furthermore, we show that these effects are not related to vitamin D serum levels, a potent inducer of LL-37 gene expression, pointing out the complex regulation of cathelicidins during septic shock.

The impact of performance status and comorbidities on the short-term prognosis of very elderly patients admitted to the ICU

BackgroundPatients ≥80 years of age are increasingly being admitted to the intensive care unit (ICU). The impact of relevant variables, such comorbidities and performance status, on short-term outcomes in the very elderly is largely unknown. Few studies address the calibration of illness severity scores (SAPS3 score) within this population. We investigated the risk factors for hospital mortality in critically ill patients ≥80 years old, emphasizing performance status and comorbidities, and assessed the calibration of SAPS3 scores in this population.Methods1129 very elderly patients admitted to a tertiary ICU in Brazil during a two-year period were retrospectively included in this study. Demographic features, reasons for admission, illness severity, comorbidities (including the Charlson Comorbidity Index) and a simplified performance status measurement were obtained. After univariate analysis, a multivariate model was created to evaluate the factors that were associated with hospital mortality. Alternatively, a conditional inference tree with recursive partitioning was constructed. Calibration of the SAPS3 scores and the multivariate model were evaluated using the Hosmer-Lemeshow test and a calibration plot. Discrimination was assessed using a receiver operating characteristics curve.ResultsOn multivariate analysis after stepwise regression, only the SAPS3 score (OR 1.08, 95% CI 1.06-1.10), Charlson Index (OR 1.16, 95% CI 1.07-1.27), performance status (OR 1.61, 95% CI 1.05-2.64 for partially dependent patients and OR 2.39, 95% CI 1.38-4.13 for fully dependent patients) and a non-full code status (OR 11.74, 95% CI 6.22-22.160) were associated with increased hospital mortality. Conditional inference tree showed that performance status and Charlson Index had the greatest influence on patients with less severe disease, whereas a non-full code status was prominent in patients with higher illness severity (SAPS3 score >61). The model obtained after logistic regression that included the before mentioned variables demonstrated better calibration and greater discrimination capability (AUC 0.86, 95% CI 0.83-0.89 versus AUC 0.81, 95% CI 0.78-0.84, respectively; p < 0.001) than the SAPS3 score alone.ConclusionsPerformance status and comorbidities are important determinants of short-term outcome in critically ill elderly patients ≥80 years old. The addition of simple background information may increase the calibration of the SAPS3 score in this population.

Relationship between acid-base status and inflammation in the critically ill.

IntroductionThere is a complex interplay between changes in acid–base components and inflammation. This manuscript aims to explore associations between plasma cytokines and chemokines and acid–base status on admission to intensive care.MethodsWe conducted a prospective cohort study in a 13-bed ICU in a tertiary-care center in Brazil. 87 unselected patients admitted to the ICU during a 2-year period were included. We measured multiple inflammatory mediators in plasma using multiplex assays and evaluated the association between mediator concentrations and acid–base variables using a variety of statistical modeling approaches, including generalized linear models, multiadaptive regression splines and principal component analysis.ResultsWe found a positive association between strong ion gap (SIG) and plasma concentrations of interleukin (IL)6, 8, 10 and tumor necrosis factor (TNF); whereas albumin was negatively associated with IL6, IL7, IL8, IL10, TNF and interferon (IFN)α. Apparent strong ion difference (SIDa) was negatively associated with IL10 and IL17. A principal component analysis including SAPS 3 indicated that the association between acid–base components and inflammatory status was largely independent of illness severity, with both increased SIG and decreased SIDa (both drivers of acidosis) associated with increased inflammation.ConclusionAcid–base variables (especially increased SIG, decreased albumin and decreased SIDa) on admission to ICU are associated with immunological activation. These findings should encourage new research into the effects of acid–base status on inflammation.

One-year survival and resource use after critical illness: impact of organ failure and residual organ dysfunction in a cohort study in Brazil

IntroductionIn this study, we evaluated the impacts of organ failure and residual dysfunction on 1-year survival and health care resource use using Intensive Care Unit (ICU) discharge as the starting point.MethodsWe conducted a historical cohort study, including all adult patients discharged alive after at least 72 h of ICU stay in a tertiary teaching hospital in Brazil. The starting point of follow-up was ICU discharge. Organ failure was defined as a value of 3 or 4 in its corresponding component of the Sequential Organ Failure Assessment score, and residual organ dysfunction was defined as a score of 1 or 2. We fit a multivariate flexible Cox model to predict 1-year survival.ResultsWe analyzed 690 patients. Mortality at 1 year after discharge was 27 %. Using multivariate modeling, age, chronic obstructive pulmonary disease, cancer, organ dysfunctions and albumin at ICU discharge were the main determinants of 1-year survival. Age and organ failure were non-linearly associated with survival, and the impact of organ failure diminished over time. We conducted a subset analysis with 561 patients (81 %) discharged without organ failure within the previous 24 h of discharge, and the number of residual organs in dysfunction remained strongly associated with reduced 1-year survival. The use of health care resources among hospital survivors was substantial within 1 year: 40 % of the patients were rehospitalized, 52 % visited the emergency department, 90 % were seen at the outpatient clinic, 14 % attended rehabilitation outpatient services, 11 % were followed by the psychological or psychiatric service and 7 % used the day hospital facility. Use of health care resources up to 30 days after hospital discharge was associated with the number of organs in dysfunction at ICU discharge.ConclusionsOrgan failure was an important determinant of 1-year outcome of critically ill survivors. Nevertheless, the impact of organ failure tended to diminish over time. Resource use after critical illness was elevated among ICU survivors, and a targeted action is needed to deliver appropriate care and to reduce the late critical illness burden.

The effects of discharge to an intermediate care unit after a critical illness: a 5-year cohort study.

PURPOSE The impact of the intermediate care unit (IMCU) on post-intensive care unit (ICU) outcomes is controversial. MATERIALS AND METHODS We analyzed admissions from January 2003 to December 2008 from a mixed ICU in a teaching hospital in Brazil with a high patient-to-nurse ratio (3.5:1 on the ICU, 11:1 on the IMCU, 20-25:1 on the ward). A retrospective propensity-matched analysis was performed with data from 690 patients who were discharged after at least 3 days of ICU stay. RESULTS Of the 690 patients, 160 (23%) were discharged to the IMCU. A total of 399 propensity-matched patients were compared: 298 were discharged to the ward and 101 were discharged to the IMCU. Ninety-day mortality rate was similar between the IMCU and ward patients (22% vs 18%, respectively, P = .37), as was the unplanned ICU readmission rate (P = .63). In a multivariate logistic regression, discharge to the IMCU had no effect on the 90-day mortality rate (P = .27). CONCLUSIONS In a resource-limited setting with a high patient-to-nurse ratio, discharge to IMCU had no impact on 90-day mortality rate and on unplanned readmission rate. The impact of discharge to the IMCU on the outcome for critically ill patients should be evaluated in further studies.

Voxel-based investigations of regional cerebral blood flow abnormalities in Alzheimer's disease using a single-detector SPECT system

PURPOSE To evaluate the feasibility of using the Statistical Parametric Mapping (SPM) program for an automated, voxel-by-voxel assessment of regional cerebral blood flow (rCBF) deficits in Alzheimers disease (AD) subjects relative to age-matched controls studied with a conventional, single-detector SPECT system. METHODS We used a databank of 99mTc-HMPAO images of 19 patients with a diagnosis of probable AD and 15 elderly healthy volunteers; data were acquired using an Orbiter-Siemens single-detector SPECT system. Using SPM, images were transformed spatially, smoothed (12mm), and the data were compared on a voxel-by-voxel basis with t-tests. RESULTS There were significant rCBF reductions in AD patients relative to controls involving regions predicted a priori to be affected in AD, namely the left temporal and parietal neocortices, and the right posterior cingulate gyrus (p<0.05, corrected for multiple comparisons). DISCUSSION The location of rCBF reductions in AD subjects in our study is consistent with the deficits detected in previous functional imaging studies of AD using higher-resolution devices. This suggests the potential usefulness of using SPM for the analysis of data acquired with single-detector SPECT systems, despite the limited sensitivity and spatial resolution of such equipment.