Rafael Barberena Moraes

Management of the Brain-Dead Organ Donor: A Systematic Review and Meta-Analysis

Background The shortage of organs is a limitation for transplantation, making the care of potential organ donors an important issue. The present systematic review and meta-analysis was carried out to assess the efficacy of interventions to stabilize hemodynamics in brain-dead donors or to improve organ function and outcomes of transplantation. Methods Medline, Embase, and Cochrane databases were searched. Of 5096 articles retrieved, 39 randomized controlled trials were selected. Twenty were included in a qualitative synthesis, providing data on 1277 patients. The main interventions described were desmopressin use, triiodothyronine and methylprednisolone replacement, fluid management, vasopressor therapy, mechanical ventilation strategies, and surgical techniques. Results Three meta-analyses were conducted: the first included two studies and showed that desmopressin administered to brain-dead patients was not advantageous with respect to early organ function in kidney recipients (relative risk, 0.97; 95% confidence interval [CI], 0.85–1.10; I2=0%; P=0.809). The second included four studies and showed that triiodothyronine did not add hemodynamic benefits versus standard management (weighted mean difference, 0.15; 95% CI, −0.13 to 0.42; I2=17.4%; P=0.304). The third meta-analysis (two studies) showed that ischemic liver preconditioning during harvesting procedures did not benefit survival (relative risk, 1.0; 95% CI, 0.93–1.08; I2=0%; P=0.459). Conclusion The present results suggest limited efficacy of interventions focusing on the management of brain-dead donors.

Phase Angle as a Prognostic Marker in Patients With Critical Illness

BACKGROUND Phase angle (PA) is interpreted as an indicator of cell membrane integrity and a prognostic indicator in some clinical situations. This study aims to evaluate PA as a prognostic marker in critically ill patients admitted to the intensive care unit (ICU) and associate this marker with length of hospital stay, mortality, and clinical scores. METHODS A cohort study was conducted with 95 patients aged ≥18 years admitted to the ICU, who were assessed in terms of prognostic indexes (Acute Physiology and Chronic Health Evaluation II [APACHE II] and Sequential Organ Failure Assessment [SOFA]), clinical evolution (ICU discharge, death, and length of ICU stay), and PA. RESULTS Patients were predominantly male (63.1%) and had a mean age of 63.7 ± 14.6 years; length of stay of 4 days (range, 3-9 days); mortality of 15.8%; mean APACHE II and SOFA scores of 17.3 ± 8.2 and 6.1 ± 3.1 points, respectively; and mean PA of 4.91 ± 1.36°. An association was observed between females and PA <5.1° (P = .035), which was the cutoff point determined from the receiver operating characteristic curve. PA was correlated with APACHE II score (r = -0.241; P = .02). This correlation became moderate only when patients without sepsis were considered (r = -0.506; P < .001). CONCLUSIONS PA seems to be a good prognostic marker for patients without sepsis. The weak correlation between PA and APACHE II score and the lack of association with other clinical outcomes are limitations for interpreting the prognostic value of PA in the entire study sample.

Vitamin D deficiency is independently associated with mortality among critically ill patients

OBJECTIVE: Studies suggest an association between vitamin D deficiency and morbidity/mortality in critically ill patients. Several issues remain unexplained, including which vitamin D levels are related to morbidity and mortality and the relevance of vitamin D kinetics to clinical outcomes. We conducted this study to address the association of baseline vitamin D levels and vitamin D kinetics with morbidity and mortality in critically ill patients. METHOD: In 135 intensive care unit (ICU) patients, vitamin D was prospectively measured on admission and weekly until discharge from the ICU. The following outcomes of interest were analyzed: 28-day mortality, mechanical ventilation, length of stay, infection rate, and culture positivity. RESULTS: Mortality rates were higher among patients with vitamin D levels <12 ng/mL (versus vitamin D levels >12 ng/mL) (32.2% vs. 13.2%), with an adjusted relative risk of 2.2 (95% CI 1.07-4.54; p< 0.05). There were no differences in the length of stay, ventilation requirements, infection rate, or culture positivity. CONCLUSIONS: This study suggests that low vitamin D levels on ICU admission are an independent risk factor for mortality in critically ill patients. Low vitamin D levels at ICU admission may have a causal relationship with mortality and may serve as an indicator for vitamin D replacement among critically ill patients.

Aldosterone secretion in patients with septic shock: a prospective study

OBJECTIVE To assess serum levels of the main factors that regulate the activation of the zona glomerulosa and aldosterone production in patients with septic shock, as well as their response to a high-dose (250 µg) adrenocorticotropic hormone (ACTH) stimulation test. SUBJECTS AND METHODS In 27 patients with septic shock, baseline levels of aldosterone, cortisol, ACTH, renin, sodium, potassium, and lactate were measured, followed by a cortrosyn test. RESULTS Renin correlated with baseline aldosterone and its variation after cortrosyn stimulation. Baseline cortisol and its variation did not correlate with ACTH. Only three patients had concomitant dysfunction of aldosterone and cortisol secretion. CONCLUSIONS Activation of the zona glomerulosa and zona fasciculata are independent. Aldosterone secretion is dependent on the integrity of the renin-angiotensin-aldosterone system, whereas cortisol secretion does not appear to depend predominantly on the hypothalamic-pituitary-adrenal axis. These results suggest that activation of the adrenal gland in critically ill patients occurs by multiple mechanisms.

De-escalation, adequacy of antibiotic therapy and culture positivity in septic patients: an observational study

Objective To evaluate the prevalence of antibiotic de-escalation in patients diagnosed with severe sepsis or septic shock at a public academic tertiary hospital and to evaluate antibiotic adequacy and culture positivity. Methods The prevalence of antibiotic de-escalation, the adequacy of antibiotic treatment and the rates of culture positivity were analyzed in patients with severe sepsis and septic shock between April and December 2013 at an intensive care unit in a tertiary university hospital. Results Among the 224 patients included in the study, de-escalation was appropriate in 66 patients (29.4%) but was implemented in 44 patients (19.6%). Among the patients who underwent de-escalation, half experienced narrowing of the antimicrobial spectrum. The mortality rate was 56.3%, with no differences between the patients with or without de-escalation (56.8% versus 56.1%; p = 0.999) nor in the length of hospital stay. Empirical antibiotic therapy was appropriate in 89% of cases. Microorganisms were isolated from total cultures in 30% of cases and from blood cultures in 26.3% of cases. Conclusion The adequacy rate of empirical antibiotic therapy was high, reflecting an active institutional policy of monitoring epidemiological profiles and institutional protocols on antimicrobial use. However, antibiotic de-escalation could have been implemented in a greater number of patients. De-escalation did not affect mortality rates.

Association between vitamin D levels and inflammatory activity in brain death: A prospective study

BACKGROUND Vitamin D insufficiency is linked to several common inflammatory disorders. Brain death (BD) causes a massive catecholamine release, leading to intense inflammatory activity. We aimed to evaluate vitamin D serum levels in brain-dead individuals in comparison to critically ill patients without BD to assess the correlation between vitamin D and cytokine levels. METHODS Sixteen brain-dead patients and 32 critically ill controls were prospectively enrolled. Blood samples from 25 brain-dead patients from a previous study were also used for vitamin D quantification. Plasma TNF, IL-1β, IL-6, IL-8, IL-10, IFN-γ and serum vitamin D levels were compared using Students t-test or one-way ANOVA. Spearmans test was used to assess the correlation between vitamin D and cytokine levels. RESULTS Mean vitamin D levels were 16.4 ± 7.9 ng/mL, with 52 patients (71.2%) classified as vitamin D deficient (serum levels < 20 ng/mL). Vitamin D levels were similar in 41 brain-dead patients as compared to control subjects (15.6 ± 6.9 ng/mL vs 17.4 ± 9.0 ng/mL; p = 0.383). Moderate direct correlations were observed between vitamin D and IL-8, IL-10, and IFN-γ in the prospective group of 16 brain-dead patients (IL-8: r = 0.5, p = 0.049; IL-10 r = 0.67, p = 0.005; IFN-γ r = 0.6, p = 0.015). Vitamin D was inversely correlated with IL-6 (r = -0.36, p = 0.044) in critically ill controls. CONCLUSIONS Vitamin D serum levels were similarly low in brain-dead and critically ill patients. In brain-dead patients, vitamin D serum levels correlated with plasma IL-8, IL-10 and IFN-γ.

Comparison of cumulative incidence analysis and Kaplan-Meier for analysis of shock reversal in patients with septic shock

INTRODUCTION Kaplan-Meier (KM) has become the most used method to evaluate time-to-event analysis, although it is unsuitable in competing event situations such as death and shock reversal. Despite that the use of this methodology is not widely disseminated, cumulative incidence analysis (CIA) is more appropriate in these situations. We used CIA and KM (with 2 different techniques of censoring) to compare shock reversal in a cohort of patients with septic shock after steroid therapy. Furthermore, we have analyzed shock reversal in responders and nonresponders to high-dose cortrosyn test (250 μg). METHODS Analysis of shock reversal in a cohort of 74 patients with septic shock at a university hospital was done. RESULTS Shock reversal by the 28th day was estimated to be 88% and 72% by KM methods and 59% by CIA. In nonresponders to cortrosyn test (Δ ≤ 9 μg/dL), shock reversal was estimated in 80% and 56% according to KM and 47% according to CIA. As for responders to cortrosyn test, shock reversal was estimated in 90% and 77% according to KM and 64% according to the CIA method. CONCLUSION Kaplan-Meier overestimates shock reversal. Cumulative incidence analysis seems to be a more appropriate method to analyze shock reversal. Future trials intended to analyze shock reversal should apply CIA.

Study protocol to assess the effectiveness and safety of a flexible family visitation model for delirium prevention in adult intensive care units: a cluster-randomised, crossover trial (The ICU Visits Study)

Introduction Flexible intensive care unit (ICU) visiting hours have been proposed as a means to improve patient-centred and family-centred care. However, randomised trials evaluating the effects of flexible family visitation models (FFVMs) are scarce. This study aims to compare the effectiveness and safety of an FFVM versus a restrictive family visitation model (RFVM) on delirium prevention among ICU patients, as well as to analyse its potential effects on family members and ICU professionals. Methods and analysis A cluster-randomised crossover trial involving adult ICU patients, family members and ICU professionals will be conducted. Forty medical-surgical Brazilian ICUs with RFVMs (<4.5 hours/day) will be randomly assigned to either an RFVM (visits according to local policies) or an FFVM (visitation during 12 consecutive hours per day) group at a 1:1 ratio. After enrolment and follow-up of 25 patients, each ICU will be switched over to the other visitation model, until 25 more patients per site are enrolled and followed. The primary outcome will be the cumulative incidence of delirium among ICU patients, measured twice a day using the Confusion Assessment Method for the ICU. Secondary outcome measures will include daily hazard of delirium, ventilator-free days, any ICU-acquired infections, ICU length of stay and hospital mortality among the patients; symptoms of anxiety and depression and satisfaction among the family members; and prevalence of burnout symptoms among the ICU professionals. Tertiary outcomes will include need for antipsychotic agents and/or mechanical restraints, coma-free days, unplanned loss of invasive devices and ICU-acquired pneumonia, urinary tract infection or bloodstream infection among the patients; self-perception of involvement in patient care among the family members; and satisfaction among the ICU professionals. Ethics and dissemination The study protocol has been approved by the research ethics committee of all participant institutions. We aim to disseminate the findings through conferences and peer-reviewed journals. Trial registration NCT02932358.

Accuracy of C - Reactive protein as a bacterial infection marker in critically immunosuppressed patients: A systematic review and meta-analysis

Background: There is a need for a better understanding of the role of C‐reactive protein (CRP) as a valid marker for the detection of bacterial infections in critically immunosuppressed patients. A high negative predictive value of CRP is also needed to rule out sepsis and bacterial infections in immunocompetent patients. However, few studies have evaluated the performance of CRP in immunocompromised hosts. The aim of the present study was to evaluate the performance of CRP as a marker of infection in critically immunosuppressed patients. Methods: The inclusion criterion was immunosuppression for which CRP was used as a bacterial infection marker. Searches were performed in the Cochrane Register, MEDLINE, EMBASE, SCOPUS, Web OF Science, LILACS and CINAHL databases. We applied the Quality Assessment of Diagnostic Accuracy Studies tool 2 (QUADAS 2) to evaluate the quality of the articles and evaluated the test accuracy parameters using hierarchical summary receiver operating characteristic (HSROC) curves and bivariate random effect models. Results: Only 13 of 21 studies produced quantitative results. We analyzed all studies using the random effects method (restricted maximum likelihood) and obtained a joint diagnostic odds ratio (DOR) of 3.04 (95% confidence interval [CI] 1.71–5.40) with heterogeneity (I2 = 91%, Q = 181.48, p < 0.001). Therefore, a bivariate model was applied. Analyzing the tuberculosis carrier, steroid user, or presence of opportunistic infection subgroups, as described in the proposal, was not possible due to the lack of information on these topics included in the articles. Conclusions: CRP appears to be a good screening tool for sepsis in critically immunosuppressed patients. Submitted PROSPERO 2015: CRD42015019329. HighlightsThere is a need for a better understanding of the role of C‐reactive protein (CRP) as a valid marker for the detection of bacterial infections in critically immunosuppressed patients. However, few studies have evaluated the performance of CRP in immunocompromised hosts;A comprehensive systematic review was conducted that included 1,418 critically immunosuppressed patients (sepsis, severe sepsis and shock septics)CRP was shown to be a useful and accurate screening test for bacterial infections, showing a sensitivity of 0.69 (0.53‐0.60), specificity of 0.76 (0.71‐0.76), and HSROC of 0.77 for the detection of bacterial infections.CRP should not be used as a single marker to diagnose sepsis but rather should be associated with clinical evaluations and other tests

Does SOFA predict outcomes better than SIRS in Brazilian ICU patients with suspected infection? A retrospective cohort study

We compared the discriminatory capacity of the sequential organ failure assessment (SOFA) versus the systemic inflammatory response syndrome (SIRS) score for predicting ICU mortality, need for and length of mechanical ventilation, ICU stay, and hospitalization in patients with suspected infection admitted to a mixed Brazilian ICU. We performed a retrospective analysis of a longitudinal ICU database from a tertiary hospital in Southern Brazil. Patients were categorized according to whether they met the criteria for sepsis according to SOFA (variation ≥2 points over the baseline clinical condition) and SIRS (SIRS score ≥2 points). From January 2008 to December 2014, 1487 patients were admitted to the ICU due to suspected infection. SOFA ≥2 identified more septic patients than SIRS ≥2 (79.0% [n=1175] vs. 68.5% [n=1020], p<0.001). There was no difference between the two scores in predicting ICU mortality (area under the receiver operating characteristic curve (AUROC)=0.64 vs. 0.64, p=0.99). SOFA ≥2 was marginally better than SIRS ≥2 in predicting need for mechanical ventilation (AUROC=0.64 vs. 0.62, p=0.001), ICU stay>7 days (AUROC=0.65 vs. 0.63, p=0.004), and length of hospitalization >10 days (AUROC=0.61 vs. 0.59, p<0.001). There was no difference between the two scores in predicting mechanical ventilation >7 days.