Association between diabetes and stress-induced hyperglycemia with skeletal muscle gene expression of INSR in critically ill patients: A prospective cohort study.

This study aimed to investigate the association between diabetes and stress-induced hyperglycemia with skeletal muscle gene expression of INSR of critically ill patients. Skeletal muscle biopsies were prospectively taken from the vastus muscle, and the expression level of INSR was analyzed using RT-qPCR. Fifty patients were included from April 2018 to September 2018. No significant differences in skeletal muscle gene expression were found between patients with or without diabetes. Similarly, there were no differences in gene expression between groups according to the presence of hypoglycemia 〈 70 mg/dl or hyperglycemia 〉 140 mg/dl. Patients with glycemic variability ≥ 40 mg/dl exhibited a downregulation of INSR compared to those with glycemic variability < 40 mg/dl (1.3 [0.01-5] vs. 2.1 [0.7 - 3.4] fold-changes, P = 0.045). The same pattern was observed when glycemic gap threshold of 80 mg/dl was used (1.4 [0.25-5] vs 1 [0.01 - 2.3] fold-changes in patients with glycemic gap < 80 mg/dl and glycemic gap ≥ 80 mg/dl respectively, P = 0.015). In conclusion, INSR was downregulated in the skeletal muscle of critically ill patients with stress-induced hyperglycemia.

Diabetes associates with mortality in critically ill patients with SARS-CoV-2 pneumonia: No diabetes paradox in COVID-19.

Background: Diabetes mellitus (DM) is not associated with increased mortality in critically ill patients, a phenomenon known as the "diabetes paradox". However, DM is a risk factor for increased mortality in patients with COVID-19. This study aims to investigate the association of DM and stress-induced hyperglycemia at intensive care unit (ICU) with mortality in this population. Methods: This is a retrospective study. Electronic medical records from patients admitted from March 2020 to September 2020 were reviewed. Primary outcome was mortality. Secondary outcomes were ICU and hospital mortality and stay, and need for mechanical ventilation and renal replacement therapy. Results: 187 patients were included. Overall mortality was 43.2%, higher in patients with DM (55.7% vs. 34%; p = 0.007), even after adjustment for age, hypertension, and disease severity. When patients were separated into groups, named normoglycemia (without DM and glycemia ≤140 mg/dL), stress-induced hyperglycemia (without DM and glycemia >140 mg/dL), and DM (previous diagnosis or HbA1c ≥ 6.5%), the mortality rate was 25.8%, 37.3%, and 55.7%, respectively (p = 0.021). Mortality was higher in patients with higher glycemic variability. No statistical difference related to secondary outcomes was observed. Conclusions: DM, hyperglycemia, and glycemic variability associated with increased mortality in critically ill patients with severe COVID-19, but did not increase the rates of other clinical outcomes. More than stress-induced hyperglycemia, DM was associated with mortality.

Prognosis of critically ill patients with extreme acidosis: A retrospective study.

OBJECTIVE: This study aims to assess the impact of different subtypes of extreme acidosis on the mortality of critically ill patients. METHODS: This retrospective cohort study included critically ill patients who were admitted to the intensive care unit (ICU) with a pH level <7. Clinical data and blood gas analyses were collected from electronic medical records. The primary outcome was in-hospital mortality. The use of vasopressors, mechanical ventilation (MV), and renal replacement therapy (RRT), the duration of MV and RRT, and the length of ICU and hospital stay were secondary outcomes. The simplified Stewart approach to acid-base disorders was used to analyze the causes of acidosis. RESULTS: A total of 231 patients with 371 arterial blood gas analyses with pH < 7 were admitted from January 2012 to December 2021 and 222 were included in the study. Out of the 222 patients analyzed, respiratory acidosis was the primary disorder in 11.3% of patients (n = 25), metabolic acidosis in 33.8% (n = 75), and mixed acidosis in 55% (n = 122). Overall mortality was 42.8% (n = 95). No significant difference was observed in mortality among patients with respiratory, metabolic, or mixed acidosis (28%, 42.7%, and 45.9%, respectively; p = 0.26). The primary disorder affected the use of vasopressors and MV, the duration of MV, and the length of ICU and hospital stay. Patients with extreme acidosis due to unmeasured anions with lactate levels of 4 mmol/L or higher had higher mortality compared with patients with lactate levels <4 mmol/L (55.6% and 27.7%, respectively; p = 0.007). CONCLUSION: Among critically ill patients with extreme acidosis, the primary disorder is not associated with mortality, but it is associated with the use of vasopressors and MV, the duration of MV, and the length of ICU and hospital stay. Additionally, hyperlactatemia is a predictor of poor prognosis in patients with extreme acidosis.

Association between neuromuscular blocking agents and the development of intensive care unit-acquired weakness (ICU-AW): A systematic review with meta-analysis and trial sequential analysis.

BACKGROUND: The present study aims to review the literature and synthesize evidence concerning the effects of the use of neuromuscular blocking agents (NMBA) regarding the development of intensive care unit-acquired weakness (ICU-AW). METHODS: This study was registered in the PROSPERO database CRD42020142916. Systematic review in PubMed, Embase, and the Cochrane Central, Randomized clinical trials (RCTs), and cohort studies with adults that reported the use of NMBA and the development of ICU-AW were included. Pre-specified subgroup analyses were performed for presence of sepsis and type of NMBA used. The quality of evidence for intervention effects was summarized. The certainty of evidence was assessed using the GRADE approach. RESULTS: We included 30 studies, four RCTs, 21 prospective and 5 retrospective cohorts, enrolling a total of 3839 patients. Most of the included studies were observational with high heterogeneity, whereas the RCTs had a high risk of bias. The use of NMBA increased the odds of developing ICU-AW (OR = 2.77 [95% CI 1.98-3.88], I2 = 62%), with low-quality of evidence. A trial sequential analysis showed the need to include 22,330 patients in order to provide evidence for either beneficial or harmful intervention effects. CONCLUSIONS: This meta-analysis suggests that the use of NMBA might be implicated in the development of ICU-AW. However, there is not enough evidence to definitively conclude about the association between the use of NMBA and the development of ICU-AW, as these results are based mostly on observational studies with high heterogeneity.

Diagnostic accuracy of multiorgan point-of-care ultrasound compared with pulmonary computed tomographic angiogram in critically ill patients with suspected pulmonary embolism.

BACKGROUND: Critically ill patients have a higher incidence of pulmonary embolism (PE) than non-critically ill patients, yet no diagnostic algorithm has been validated in this population, leading to the overuse of pulmonary artery computed tomographic angiogram (CTA). This study aimed to comparatively evaluate the diagnostic accuracy of point-of-care ultrasound (POCUS) combined with laboratory data versus CTA in predicting PE in critically ill patients. METHODS: A prospective diagnostic accuracy study. Critically ill patients with suspected acute PE undergoing CTA were prospectively enrolled. Demographic and clinical data were collected from electronic medical records. Blood samples were collected, and the Wells and revised Geneva scores were calculated. Standardized multiorgan POCUS and CTA were performed. The discriminatory power of multiorgan POCUS combined with biochemical markers was tested using ROC curves, and multivariate analysis was performed. RESULTS: A total of 88 patients were included, and 37 (42%) had PE. Multivariate analysis showed a relative risk (RR) of PE of 2.79 (95% CI, 1.61-4.84) for the presence of right ventricular (RV) dysfunction, of 2.54 (95% CI, 0.89-7.20) for D-dimer levels >1000 ng/mL, and of 1.69 (95% CI, 1.12-2.63) for the absence of an alternative diagnosis to PE on lung POCUS or chest radiograph. The combination with the highest diagnostic accuracy for PE included the following variables: 1- POCUS transthoracic echocardiography with evidence of RV dysfunction; 2- lung POCUS or chest radiograph without an alternative diagnosis to PE; and 3- plasma D-dimer levels >1000 ng/mL. Combining these three findings resulted in an area under the curve of 0.85 (95% CI, 0.77-0.94), with 50% sensitivity and 96% specificity. CONCLUSIONS: Multiorgan POCUS combined with laboratory data has acceptable diagnostic accuracy for PE compared with CTA. The combined use of these methods might reduce CTA overuse in critically ill patients.

Wells and Geneva Scores Are Not Reliable Predictors of Pulmonary Embolism in Critically Ill Patients: A Retrospective Study.

BACKGROUND: Critically ill patients are at high risk for pulmonary embolism (PE). Specific PE prediction rules have not been validated in this population. The present study assessed the Wells and revised Geneva scoring systems as predictors of PE in critically ill patients. METHODS: Pulmonary computed tomographic angiograms (CTAs) performed for suspected PE in critically ill adult patients were retrospectively identified. Wells and revised Geneva scores were calculated based on information from medical records. The reliability of both scores as predictors of PE was determined using receiver operating characteristic (ROC) curve analysis. RESULTS: Of 138 patients, 42 (30.4%) were positive for PE based on pulmonary CTA. Mean Wells score was 4.3 (3.5) in patients with PE versus 2.7 (1.9) in patients without PE (P < .001). Revised Geneva score was 5.8 (3.3) versus 5.1 (2.5) in patients with versus without PE (P = .194). According to the Wells and revised Geneva scores, 56 (40.6%) patients and 49 (35.5%) patients, respectively, were considered as low probability for PE. Of those considered as low risk by the Wells score, 15 (26.8%) had filling defects on CTA, including 2 patients with main pulmonary artery embolism. The area under the ROC curve was 0.634 for the Wells score and 0.546 for the revised Geneva score. Wells score >4 had a sensitivity of 40%, specificity of 87%, positive predictive value of 59%, and negative predictive value of 77% to predict risk of PE. CONCLUSIONS: In this population of critically ill patients, Wells and revised Geneva scores were not reliable predictors of PE.

Association of multiple glycemic parameters at intensive care unit admission with mortality and clinical outcomes in critically ill patients.

The aim of the present study was to investigate the association of multiple glycemic parameters at intensive care unit (ICU) admission with outcomes in critically ill patients. Critically ill adults admitted to ICU were included prospectively in the study and followed for 180 days until hospital discharge or death. Patients were assessed for glycemic gap, hypoglycemia, hyperglycemia, glycemic variability, and stress hyperglycemia ratio (SHR). A total of 542 patients were enrolled (30% with preexisting diabetes). Patients with glycemic gap >80 mg/dL had increased need for renal replacement therapy (RRT; 37.7% vs. 23.7%, p = 0.025) and shock incidence (54.7% vs. 37.4%, p = 0.014). Hypoglycemia was associated with increased mortality (54.8% vs. 35.8%, p = 0.004), need for RRT (45.1% vs. 22.3%, p < 0.001), mechanical ventilation (MV; 72.6% vs. 57.5%, p = 0.024), and shock incidence (62.9% vs. 35.8%, p < 0.001). Hyperglycemia increased mortality (44.3% vs. 34.9%, p = 0.031). Glycemic variability >40 mg/dL was associated with increased need for RRT (28.3% vs. 14.4%, p = 0.002) and shock incidence (41.4% vs.31.2%, p = 0.039). In this mixed sample of critically ill subjects, including patients with and without preexisting diabetes, glycemic gap, glycemic variability, and SHR were associated with worse outcomes, but not with mortality. Hypoglycemia and hyperglycemia were independently associated with increased mortality.

Renal Outcomes of Vasopressin and Its Analogs in Distributive Shock: A Systematic Review and Meta-Analysis of Randomized Trials.

OBJECTIVES: To systematically review the literature and synthesize evidence concerning the effects of vasopressin and its analogs compared with other vasopressors in distributive shock, focusing on renal outcomes. DATA SOURCES: We performed a systematic review in MEDLINE, Embase, Cochrane Central, and Clinicaltrials.gov databases. STUDY SELECTION: Randomized clinical trials that compared vasopressin and its analogs with other vasopressors and reported renal outcomes in adult patients with distributive shock. DATA EXTRACTION: Paired reviewers independently screened citations, conducted data extraction and assessed risk of bias. Three prespecified subgroup analyses were conducted. Three main outcomes related to acute renal failure were analyzed: the need for renal replacement therapy, acute kidney injury incidence, and acute kidney injury-free days. I test was used to evaluate heterogeneity between studies. Substantial heterogeneity was defined as I greater than 50%. A random-effects model with Mantel-Haenszel weighting was used for all analyses. Heterogeneity was explored using subgroup analysis. The quality of evidence for intervention effects was summarized using Grading of Recommendations Assessment, Development, and Evaluation methodology. This study was registered in the PROSPERO database (CRD42017054324). DATA SYNTHESIS: Three-thousand twenty-six potentially relevant studies were identified, and 30 articles were reviewed in full. Seventeen studies met the inclusion criteria, including a total of 2,833 individuals. Of these, 11 studies (2,691 individuals) were suitable for quantitative meta-analysis. Overall, the evidence was of low to moderate quality. Patients who received vasopressin and its analogs had a reduced need for renal replacement therapy (odds ratio, 0.59 [0.37-0.92]; p = 0.02; I = 49%) and a lower acute kidney injury incidence (odds ratio, 0.58 [0.37-0.92]; p = 0.02; I = 63%). These results should be interpreted with caution, due to excessive heterogeneity. Acute kidney injury-free data was not pooled, since the small number of studies and extreme heterogeneity. CONCLUSIONS: In patients with distributive shock, vasopressin and its analogs use is associated with a reduced need for renal replacement therapy and lower acute kidney injury incidence. These results are supported by high risk of bias evidence.

Brain Death-Induced Inflammatory Activity is Similar to Sepsis-Induced Cytokine Release.

Brain death (BD) is associated with a systemic inflammation leading to worse graft outcomes. This study aimed to compare plasma cytokine values between brain-dead and critically ill patients, including septic and non-septic controls, and evaluate cytokine release kinetics in BD. Sixteen brain-dead and 32 control patients (16 with and 16 without sepsis) were included. Plasma cytokines were measured by magnetic bead assay after the first clinical exam consistent with BD and every 6 hours thereafter, and at the time of study entry in the control group. The values for IL-8 and IFN-γ were higher in brain-dead and septic patients than in non-septic patients [IL-8: 80.3 (18.7-169.6) vs. 68.2 (22.4-359.4) vs. 16.4 (9.2-42.7) pg/mL; P = 0.006; IFN-γ: 2.8 (1.6-6.1) vs. 3.4 (1.2-9.0) vs. 0.5 (0.5-1.8) pg/mL; P = 0.012]. TNF showed a clear tendency to increase in brain-dead patients [2.7 (1.0-4.8) vs. 1.0 (1.0-5.6) vs. 1.0 (1.0-1.0) pg/mL; P = 0.051], and IL-6 values were higher in brain-dead patients than in non-septic controls [174.5 (104.9-692.5) vs. 13.2 (7.3-38.6) pg/mL; P = 0.002]. These differences remained even after excluding brain-dead patients who also had sepsis ( n = 3). IL-1ß and IL-10 values increased from baseline to time point 2 (∼6 hours later) [IL-1ß: 5.39 (1.93-16.89) vs. 7.11 (1.93-29.13) pg/mL; P = 0.012; IL-10: 8.78 (3.62-16.49) vs. 15.73 (5.49-23.98) pg/mL; P = 0.009]. BD-induced and sepsis-induced plasma cytokine values were similarly high, and both were higher than the observed in non-septic critically ill patients.

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-1ß, IL-6, IL-8, IL-10, IFN-γ and serum vitamin D levels were compared using Student's t-test or one-way ANOVA. Spearman's test was used to assess the correlation between vitamin D and cytokine levels. RESULTS: Mean vitamin D levels were 16.4 ±â€¯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 ±â€¯6.9 ng/mL vs 17.4 ±â€¯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.

UCP2 Expression Is Increased in Pancreas From Brain-Dead Donors and Involved in Cytokine-Induced ß Cells Apoptosis.

BACKGROUND: Systemic inflammation associated with brain death (BD) decreases islet yield and quality, negatively affecting outcomes of human islet transplantation. A recent study from our group showed an increased expression of uncoupling protein-2 (UCP2) in pancreas from rats with BD as compared with controls. UCP2 is located in the mitochondrial inner membrane and regulates production of reactive oxygen species and glucose-stimulated insulin secretion. It has been suggested that UCP2 also plays a role in ß cell apoptosis, but these findings remain controversial. METHODS: We have presently performed a case-control study to assess UCP2 expression in pancreas from BD donors (cases) and subjects who underwent pancreatectomy (controls). We next investigated the role of Ucp2 in cytokine-induced apoptosis of rat insulin-producing INS-1E cells. RESULTS: UCP2 gene expression was higher in pancreas from BD donors compared with controls (1.73 ± 0.93 vs 0.75 ± 0.66; fold change, P < 0.05). Ucp2 knockdown (80% at the protein and messenger RNA levels) reduced by 30% cytokine-induced apoptosis and nitric oxide production in INS-1E cells. This protection was associated with decreased expression of cleaved (activated) caspases 9 and 3, suggesting that Ucp2 knockdown interferes with cytokine triggering of the intrinsic apoptotic pathway. Moreover, both messenger RNA and protein concentrations of the antiapoptotic protein Bcl-2 were increased after Ucp2 knockdown in INS-1E cells. CONCLUSIONS: These data suggest that UCP2 has an apoptotic effect in ß cells via regulation of the intrinsic pathway of apoptosis.

Neuron-enriched RNA-binding Proteins Regulate Pancreatic Beta Cell Function and Survival.

Pancreatic beta cell failure is the central event leading to diabetes. Beta cells share many phenotypic traits with neurons, and proper beta cell function relies on the activation of several neuron-like transcription programs. Regulation of gene expression by alternative splicing plays a pivotal role in brain, where it affects neuronal development, function, and disease. The role of alternative splicing in beta cells remains unclear, but recent data indicate that splicing alterations modulated by both inflammation and susceptibility genes for diabetes contribute to beta cell dysfunction and death. Here we used RNA sequencing to compare the expression of splicing-regulatory RNA-binding proteins in human islets, brain, and other human tissues, and we identified a cluster of splicing regulators that are expressed in both beta cells and brain. Four of them, namely Elavl4, Nova2, Rbox1, and Rbfox2, were selected for subsequent functional studies in insulin-producing rat INS-1E, human EndoC-ßH1 cells, and in primary rat beta cells. Silencing of Elavl4 and Nova2 increased beta cell apoptosis, whereas silencing of Rbfox1 and Rbfox2 increased insulin content and secretion. Interestingly, Rbfox1 silencing modulates the splicing of the actin-remodeling protein gelsolin, increasing gelsolin expression and leading to faster glucose-induced actin depolymerization and increased insulin release. Taken together, these findings indicate that beta cells share common splicing regulators and programs with neurons. These splicing regulators play key roles in insulin release and beta cell survival, and their dysfunction may contribute to the loss of functional beta cell mass in diabetes.

Brain death-induced inflammatory activity in human pancreatic tissue: a case-control study.

BACKGROUND: Long-term insulin independence after islet transplantation depends on engraftment of a large number of islets. However, the yield of pancreatic islets from brain-dead donors is negatively affected by the up-regulation of inflammatory mediators. Brain death is also believed to increase tissue factor (TF) expression, contributing to a low rate of engraftment. METHODS: We conducted a case-control study to assess brain death-induced inflammatory effects in human pancreas. Seventeen brain-dead patients and 20 control patients undergoing pancreatectomy were studied. Serum tumor necrosis factor (TNF), interleukin (IL) 6, IL-1ß, interferon (IFN) γ, and TF were measured using enzyme-linked immunosorbent assay kits. Gene expressions of these cytokines and TF were evaluated by reverse transcriptase quantitative polymerase chain reaction. Protein quantification was performed by immunohistochemistry in paraffin-embedded pancreas sections. RESULTS: Brain-dead patients had higher serum concentrations of TNF and IL-6 and increased TNF protein levels compared to controls. The groups had similar TNF, IL-6, IL-1ß, and IFN-γ messenger RNA levels in pancreatic tissue. Reverse transcriptase quantitative polymerase chain reaction revealed TF messenger RNA up-regulation in controls. Immunohistochemical analyses showed that brain-dead patients had increased TNF protein levels compared to controls. CONCLUSIONS: Brain death induces inflammation evidenced by the up-regulation of TNF in serum and pancreatic tissue. Blocking the expression of key inflammatory mediators in brain-dead donors should be evaluated as a new approach to improve the outcomes of islet transplantation.

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; I(2) = 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; I(2) = 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; I(2) = 0%; P = 0.459). CONCLUSION: The present results suggest limited efficacy of interventions focusing on the management of brain-dead donors.

Manuseio do potencial doador de múltiplos órgãos / Care of the potential organ donor

JUSTIFICATIVA E OBJETIVOS: O transplante de órgãos sólidos vem sendo considerado o tratamento de eleição para várias doenças terminais que afetam rim, pâncreas, fígado, coração e pulmão. Atualmente, o maior limitante às cirurgias dos transplantes é a escassez de órgãos. O objetivo deste estudo foi revisar aspectos fisiopatológicos da morte encefálica e resumir estratégias terapêuticas atuais, para o cuidado otimizado do doador, do que depende o sucesso dos transplantes. CONTEÚDO: A morte encefálica é uma síndrome inflamatória que pode rapidamente produzir alterações deletérias nos órgãos dos potenciais doadores. Esse contexto de instabilidade hemodinâmica, metabólica e eletrolítica, exige do intensivista cuidados especiais com o doador de múltiplos órgãos. CONCLUSÔES: O adequado conhecimento da complexa fisiopatologia envolvendo a morte encefálica é de fundamental importância para que se implemente de forma racional um protocolo de manuseio agressivo do potencial doador, o que certamente resultará num aumento de órgãos captados e do número de órgãos captados por doador, além da redução das taxas de disfunção primária dos enxertos transplantados.

BACKGROUND AND OBJECTIVES: Organ transplantation has long been considered the treatment of choice for many end-stage organ diseases. As soon as transplantation turned to be a viable therapy, organ shortage became the major limitation for the procedures. Nowadays, there is an increasing imbalance between organ supply and demand. Apparently, the most promising way to increase organ supply is optimizing the care for the brain death organ donor. The objective of this manuscript was to review the pathophysiological aspects and therapeutic strategies for the optimized care of the potential organ donor. CONTENTS: Brain death causes a massive catecholamine release, inducing a variety of deleterious effects that can threat organ perfusion. Studies have documented a sudden decrease in cortisol, insulin, thyroid and pituitary hormones. In this scenario of hemodynamic and metabolic instability, a special attention to the multiple organ donor support is required. CONCLUSIONS: An extensive knowledge of the complex brain death pathophysiology is extremely important for the implementation of rational aggressive management protocols of the potential organ donor, aiming to increase the number of harvested organs and the number of organs harvested per donor.

Entrevista familiar e consentimento / Family approach and consent for organ donation

JUSTIFICATIVA E OBJETIVOS: Desde que o transplante de órgãos firmou-se como o tratamento de escolha para muitas doenças em estágio final, a escassez de órgãos vem se tornando um problema progressivamente maior, à medida que pacientes acumulam-se nas listas de espera. O objetivo deste estudo foi revisar questões relativas à melhor prática de abordagem da família do doador e como esses e outros aspectos referentes ao processo de doação podem interferir nas taxas de consentimento CONTEÚDO: A despeito do crescente aumento de doadores vivos, o doador cadavérico com morte encefálica continua sendo a principal fonte de órgãos para transplante e a única fonte significativa de órgãos extra-renais. Alguns fatores têm sido identificados como empecilhos no processo de doação, dos quais os maiores são a não-identificação do paciente em morte encefálica, o manuseio inadequado do doador e a recusa da família em doar os órgãos. Aumentar as taxas de consentimento para doação parece ser, no momento, o melhor instrumento para diminuir o problema da escassez de órgãos. CONCLUSÕES: Muitos aspectos estão envolvidos na decisão de uma família em doar os órgãos de seus familiares. Técnicas especiais de abordagem e profissionais bem treinados em entrevista familiar influenciam nas taxas de consentimento.

BACKGROUND AND OBJECTIVES: Since organ transplantation has become the treatment of choice for several end-stage diseases, organ shortage is the most important barrier for the procedures and waiting lists are increasing out of proportion. The objective of this study was to review the best practices concerning family referral and how these issues and others aspects of the donation process can influence consent rates. CONTENTS: Despite the growing number of live donors, the brain death donor continuous to be the major source of organs for transplantation and the only source of extra-renal organs. Many problems have been identified in the donation process, including non-identification of the brain death donor, inadequate care of the donors and family refusal to donation. Increasing the consent rate for donation seems to be a good alternative to reduce organ shortage. CONCLUSIONS: Family decision to donate organs is influenced by several aspects. Highly trained professionals in family referral can affect consent rates.

[Family approach and consent for organ donation]. / Entrevista familiar e consentimento.

BACKGROUND AND OBJECTIVES: Since organ transplantation has become the treatment of choice for several end-stage diseases, organ shortage is the most important barrier for the procedures and waiting lists are increasing out of proportion. The objective of this study was to review the best practices concerning family referral and how these issues and others aspects of the donation process can influence consent rates. CONTENTS: Despite the growing number of live donors, the brain death donor continuous to be the major source of organs for transplantation and the only source of extra-renal organs. Many problems have been identified in the donation process, including non-identification of the brain death donor, inadequate care of the donors and family refusal to donation. Increasing the consent rate for donation seems to be a good alternative to reduce organ shortage. CONCLUSIONS: Family decision to donate organs is influenced by several aspects. Highly trained professionals in family referral can affect consent rates.

[Care of the potential organ donor]. / Manuseio do potencial doador de múltiplos órgãos.

BACKGROUND AND OBJECTIVES: Organ transplantation has long been considered the treatment of choice for many end-stage organ diseases. As soon as transplantation turned to be a viable therapy, organ shortage became the major limitation for the procedures. Nowadays, there is an increasing imbalance between organ supply and demand. Apparently, the most promising way to increase organ supply is optimizing the care for the brain death organ donor. The objective of this manuscript was to review the pathophysiological aspects and therapeutic strategies for the optimized care of the potential organ donor. CONTENTS: Brain death causes a massive catecholamine release, inducing a variety of deleterious effects that can threat organ perfusion. Studies have documented a sudden decrease in cortisol, insulin, thyroid and pituitary hormones. In this scenario of hemodynamic and metabolic instability, a special attention to the multiple organ donor support is required. CONCLUSIONS: An extensive knowledge of the complex brain death pathophysiology is extremely important for the implementation of rational aggressive management protocols of the potential organ donor, aiming to increase the number of harvested organs and the number of organs harvested per donor.

Valor da enolase específica do neurônio como indicador de prognóstico pós-parada cardiorrespiratória / Serum neuron-specific enolase as a prognostic marker after a cardiac arrest

JUSTIFICATIVA E OBJETIVOS: A parada cardíaca é um estado de grave hipoperfusão cerebral. Os pacientes que sobrevivem a uma reanimação cardiorrespiratória estão sob grande risco de vir a morrer ou desenvolver lesão cerebral incapacitante, inclusive estado vegetativo persistente. Uma definição precoce do prognóstico desses pacientes tem implicações éticas e econômicas. O objetivo desse estudo foi revisar o valor prognóstico da Enolase Específica do Neurônio (NSE) em predizer precocemente os desfechos de pacientes após uma parada cardíaca. CONTEÚDO: A lesão cerebral permanente é a complicação mais temida de uma reanimação cardíaca prolongada. Muitos estudos têm tentado isolar fatores prognósticos que possam estar associados com desfechos clínicos em pacientes sobreviventes de parada cardíaca. Indicadores bioquímicos de morte neuronal parecem promissores nesse cenário. Nesse contexto, a NSE vem sendo estudada em pacientes reanimados de paradas cardíacas e níveis elevados dessa enzima sugerem lesão encefálica mais extensa e estão associados a desfechos clínicos desfavoráveis. CONCLUSÕES: Os desfechos depois de uma parada cardíaca são determinados principalmente pelo grau de lesão cerebral isquêmica e medidas precoces de NSE sérica podem ser um método adjunto de grande valor na avaliação prognóstica desses pacientes.

BACKGROUND AND OBJECTIVES: Cardiac arrest is a state of severe cerebral perfusion deficit. Patients recovering from a cardiopulmonary resuscitation are at great risk of subsequent death or incapacitating neurologic injury, including persistent vegetative state. The early definition of prognosis for these patients has ethical and economic implications. The main purpose of this manuscript was to review the prognostic value of serum Neuron-Specific Enolase (NSE) in predicting outcomes in patients early after a cardiac arrest. CONTENTS: Severe neurologic disability is the most feared complication after a cardiac arrest. Many studies are trying to find prognostic markers that can be associated with outcomes in patients surviving a cardiac arrest. Biochemical markers of neuronal injury seem to be promising in this scenario. Therefore, NSE levels have been studied in patients after a cardiac arrest and high enzyme levels suggest more extensive brain damage and are associated with unfavorable clinical outcomes. CONCLUSIONS: Outcome after a cardiac arrest is mostly determined by the degree of hypoxic brain damage and early determinations of serum NSE level can be a valuable ancillary method for assessing outcome in these patients.

Serum neuron-specific enolase as early predictor of outcome after in-hospital cardiac arrest: a cohort study.

INTRODUCTION: Outcome after cardiac arrest is mostly determined by the degree of hypoxic brain damage. Patients recovering from cardiopulmonary resuscitation are at great risk of subsequent death or severe neurological damage, including persistent vegetative state. The early definition of prognosis for these patients has ethical and economic implications. The main purpose of this study was to investigate the prognostic value of serum neuron-specific enolase (NSE) in predicting outcomes in patients early after in-hospital cardiac arrest. METHODS: Forty-five patients resuscitated from in-hospital cardiac arrest were prospectively studied from June 2003 to January 2005. Blood samples were collected, at any time between 12 and 36 hours after the arrest, for NSE measurement. Outcome was evaluated 6 months later with the Glasgow outcome scale (GOS). Patients were divided into two groups: group 1 (unfavorable outcome) included GOS 1 and 2 patients; group 2 (favorable outcome) included GOS 3, 4 and 5 patients. The Mann-Whitney U test, Student's t test and Fisher's exact test were used to compare the groups. RESULTS: The Glasgow coma scale scores were 6.1 +/- 3 in group 1 and 12.1 +/- 3 in group 2 (means +/- SD; p < 0.001). The mean time to NSE sampling was 20.2 +/- 8.3 hours in group 1 and 28.4 +/- 8.7 hours in group 2 (p = 0.013). Two patients were excluded from the analysis because of sample hemolysis. At 6 months, favorable outcome was observed in nine patients (19.6%). Thirty patients (69.8%) died and four (9.3%) remained in a persistent vegetative state. The 34 patients (81.4%) in group 1 had significantly higher NSE levels (median 44.24 ng/ml, range 8.1 to 370) than those in group 2 (25.26 ng/ml, range 9.28 to 55.41; p = 0.034). CONCLUSION: Early determination of serum NSE levels is a valuable ancillary method for assessing outcome after in-hospital cardiac arrest.