Role of aspirin, beta-blocker, statins, and heparin therapy in septic patients under mechanical ventilation: a narrative review.

Sepsis is the main cause of death among patients admitted to intensive care units. Management of sepsis includes fluid resuscitation, vasopressors, intravenous antimicrobials, source control, mechanical ventilation, and others. New insights into the potential benefits of non-antimicrobial drugs in sepsis have evolved based on the pathophysiology of the disease and the mechanism of action of some drugs, but the findings are still controversial. In this study, we aimed to evaluate the effect of beta-blockers, aspirin, statins, and heparin as adjunctive treatments in septic patients under mechanical ventilation with non-cardiovascular diseases and their effect on mortality. We searched PubMed with relevant keywords (beta-blockers, aspirin, statins, or heparin, and critically ill or sepsis) for the last 10 years and some personal collection of relevant articles, and then we assessed studies according to prespecified inclusion and exclusion criteria. Our results show that beta-blockers, aspirin, and heparin may have promising feedback on reducing mortality. However, new well-controlled, randomized, multicenter studies are needed to confirm that, and multiple issues regarding their usage need to be addressed. On the other hand, the feedback regarding the effectiveness of statins was not as strong as that of the other drugs studied, and we suggest that further research is needed to confirm these results.

Epidemiologia e desfecho dos pacientes de alto risco cirúrgico admitidos em unidades de terapia intensiva no Brasil / Epidemiology and outcome of high-surgical-risk patients admitted to an intensive care unit in Brazil

RESUMO Objetivo: Definir o perfil epidemiológico e os principais determinantes de morbimortalidade dos pacientes cirúrgicos não cardíacos de alto risco no Brasil. Métodos: Estudo prospectivo, observacional e multicêntrico. Todos os pacientes cirúrgicos não cardíacos admitidos nas unidades de terapia intensiva, ou seja, considerados de alto risco, no período de 1 mês, foram avaliados e acompanhados diariamente por, no máximo, 7 dias na unidade de terapia intensiva, para determinação de complicações. As taxas de mortalidade em 28 dias de pós-operatório, na unidade de terapia intensiva e hospitalar foram avaliadas. Resultados: Participaram 29 unidades de terapia intensiva onde foram realizadas cirurgias em 25.500 pacientes, dos quais 904 (3,5%) de alto risco (intervalo de confiança de 95% - IC95% 3,3% - 3,8%), tendo sido incluídos no estudo. Dos pacientes envolvidos, 48,3% eram de unidades de terapia intensiva privadas e 51,7% de públicas. O tempo de internação na unidade de terapia intensiva foi de 2,0 (1,0 - 4,0) dias e hospitalar de 9,5 (5,4 - 18,6) dias. As taxas de complicações foram 29,9% (IC95% 26,4 - 33,7) e mortalidade em 28 dias pós-cirurgia 9,6% (IC95% 7,4 - 12,1). Os fatores independentes de risco para complicações foram Simplified Acute Physiology Score 3 (SAPS 3; razão de chance − RC = 1,02; IC95% 1,01 - 1,03) e Sequential Organ Failure Assessment Score (SOFA) da admissão na unidade de terapia intensiva (RC =1,17; IC95% 1,09 - 1,25), tempo de cirurgia (RC = 1,001; IC95% 1,000 - 1,002) e cirurgias de emergências (RC = 1,93; IC95% 1,10 - 3,38). Em adição, foram associados com mortalidade em 28 dias idade (RC = 1,032; IC95% 1,011 - 1,052) SAPS 3 (RC = 1,041; IC95% 1,107 - 1,279), SOFA (RC = 1,175; IC95% 1,069 - 1,292) e cirurgias emergenciais (RC = 2,509; IC95% 1,040 - 6,051). Conclusão: Pacientes com escores prognósticos mais elevados, idosos, tempo cirúrgico e cirurgias emergenciais estiveram fortemente associados a maior mortalidade em 28 dias e mais complicações durante permanência em unidade de terapia intensiva.

ABSTRACT Objective: To define the epidemiological profile and the main determinants of morbidity and mortality in noncardiac high surgical risk patients in Brazil. Methods: This was a prospective, observational and multicenter study. All noncardiac surgical patients admitted to intensive care units, i.e., those considered high risk, within a 1-month period were evaluated and monitored daily for a maximum of 7 days in the intensive care unit to determine complications. The 28-day postoperative, intensive care unit and hospital mortality rates were evaluated. Results: Twenty-nine intensive care units participated in the study. Surgeries were performed in 25,500 patients, of whom 904 (3.5%) were high-risk (95% confidence interval - 95%CI 3.3% - 3.8%) and were included in the study. Of the participating patients, 48.3% were from private intensive care units, and 51.7% were from public intensive care units. The length of stay in the intensive care unit was 2.0 (1.0 - 4.0) days, and the length of hospital stay was 9.5 (5.4 - 18.6) days. The complication rate was 29.9% (95%CI 26.4 - 33.7), and the 28-day postoperative mortality rate was 9.6% (95%CI 7.4 - 12.1). The independent risk factors for complications were the Simplified Acute Physiology Score 3 (SAPS 3; odds ratio - OR = 1.02; 95%CI 1.01 - 1.03) and Sequential Organ Failure Assessment Score (SOFA) on admission to the intensive care unit (OR = 1.17; 95%CI 1.09 - 1.25), surgical time (OR = 1.001, 95%CI 1.000 - 1.002) and emergency surgeries (OR = 1.93, 95%CI, 1.10 - 3.38). In addition, there were associations with 28-day mortality (OR = 1.032; 95%CI 1.011 - 1.052), SAPS 3 (OR = 1.041; 95%CI 1.107 - 1.279), SOFA (OR = 1.175, 95%CI 1.069 - 1.292) and emergency surgeries (OR = 2.509; 95%CI 1.040 - 6.051). Conclusion: Higher prognostic scores, elderly patients, longer surgical times and emergency surgeries were strongly associated with higher 28-day mortality and more complications during the intensive care unit stay.

Acute bag-valve breathing maneuvers plus manual chest compression is safe during stable septic shock: a randomized clinical trial. / Uso da hiperinsuflação manual combinada com pressão expiratória positiva e compressão torácica é seguro durante o choque séptico estável: um estudo clínico randomizado.

OBJECTIVE:: To evaluate the effects of bag-valve breathing maneuvers combined with standard manual chest compression techniques on safety, hemodynamics and oxygenation in stable septic shock patients. DESIGN:: A parallel, assessor-blinded, randomized trial of two groups. A computer-generated list of random numbers was prepared by an independent researcher to allocate treatments. SETTING:: The Intensive Care Unit at Hospital São Lucas, Pontifícia Universidade Católica do Rio Grande do Sul. PARTICIPANTS:: Fifty-two subjects were assessed for eligibility, and 32 were included. All included subjects (n = 32) received the allocated intervention (n = 19 for the Experimental Group and n = 13 for the Control Group). INTERVENTION:: Twenty minutes of bag-valve breathing maneuvers combined with manual chest compression techniques (Experimental Group) or chest compression, as routinely used at our intensive care unit (Control Group). Follow-up was performed immediately after and at 30 minutes after the intervention. MAIN OUTCOME MEASURE:: Mean artery pressure. RESULTS:: All included subjects completed the trial (N = 32). We found no relevant effects on mean artery pressure (p = 0.17), heart rate (p = 0.50) or mean pulmonary artery pressure (p = 0.89) after adjusting for subject age and weight. Both groups were identical regarding oxygen consumption after the data adjustment (p = 0.84). Peripheral oxygen saturation tended to increase over time in both groups (p = 0.05), and there was no significant association between cardiac output and venous oxygen saturation (p = 0.813). No clinical deterioration was observed. CONCLUSION:: A single session of bag-valve breathing maneuvers combined with manual chest compression is hemodynamically safe for stable septic-shocked subjects over the short-term.

Uso da hiperinsuflação manual combinada com pressão expiratória positiva e compressão torácica é seguro durante o choque séptico estável: um estudo clínico randomizado / Acute bag-valve breathing maneuvers plus manual chest compression is safe during stable septic shock: a randomized clinical trial

RESUMO Objetivo: Avaliar os efeitos de manobras de hiperinsuflação manual combinadas com pressão expiratória positiva associadas com técnicas padrão de compressão manual do tórax, com relação à segurança, à hemodinâmica e à oxigenação em pacientes com choque séptico estável. Delineamento: Este foi um estudo com dois grupos paralelos, randomizado e com avaliador cego. Um pesquisador independente preparou uma lista de randomização gerada por computador para alocação dos tratamentos. Local: Unidade de terapia intensiva do Hospital São Lucas, Pontifícia Universidade Católica do Rio Grande do Sul. Participantes: Foram avaliados 52 indivíduos quanto à elegibilidade e, destes, 32 pacientes foram incluídos no estudo. Todos os indivíduos incluídos (n = 32) receberam a intervenção alocada (n = 19 para o Grupo Experimental e n = 13 para o Grupo Controle). Intervenção: Vinte minutos de manobras de hiperinsuflação manual combinadas com pressão expiratória positiva associadas com técnicas padrão de compressão manual do tórax (Grupo Experimental) ou compressão do tórax, conforme o uso rotineiro de nossa unidade de terapia intensiva (Grupo Controle). Foi realizado seguimento imediatamente após e 30 minutos após a intervenção. Principal métrica de desfecho: Pressão arterial média. Resultados: Todos os indivíduos inscritos concluíram o estudo (n = 32). Não identificamos efeitos relevantes na pressão arterial média (p = 0,17), frequência cardíaca (p = 0,50) ou pressão média da artéria pulmonar (p = 0,89) após ajuste quanto à idade e ao peso do participante. Após ajuste dos dados, ambos os grupos foram idênticos com relação ao consumo de oxigênio (p = 0,84). A saturação periférica de oxigênio tendeu a aumentar com o tempo em ambos os grupos (p = 0,05), e não ocorreu associação significante entre o débito cardíaco e a saturação venosa de oxigênio (p = 0,813). Não se observou deterioração clínica. Conclusão: Uma única sessão de manobras de hiperinsuflação manual combinadas com pressão expiratória positiva associadas com técnicas padrão de compressão manual do tórax é hemodinamicamente segura em curto prazo para pacientes com choque séptico estável.

ABSTRACT Objective: To evaluate the effects of bag-valve breathing maneuvers combined with standard manual chest compression techniques on safety, hemodynamics and oxygenation in stable septic shock patients. Design: A parallel, assessor-blinded, randomized trial of two groups. A computer-generated list of random numbers was prepared by an independent researcher to allocate treatments. Setting: The Intensive Care Unit at Hospital São Lucas, Pontifícia Universidade Católica do Rio Grande do Sul. Participants: Fifty-two subjects were assessed for eligibility, and 32 were included. All included subjects (n = 32) received the allocated intervention (n = 19 for the Experimental Group and n = 13 for the Control Group). Intervention: Twenty minutes of bag-valve breathing maneuvers combined with manual chest compression techniques (Experimental Group) or chest compression, as routinely used at our intensive care unit (Control Group). Follow-up was performed immediately after and at 30 minutes after the intervention. Main outcome measure: Mean artery pressure. Results: All included subjects completed the trial (N = 32). We found no relevant effects on mean artery pressure (p = 0.17), heart rate (p = 0.50) or mean pulmonary artery pressure (p = 0.89) after adjusting for subject age and weight. Both groups were identical regarding oxygen consumption after the data adjustment (p = 0.84). Peripheral oxygen saturation tended to increase over time in both groups (p = 0.05), and there was no significant association between cardiac output and venous oxygen saturation (p = 0.813). No clinical deterioration was observed. Conclusion: A single session of bag-valve breathing maneuvers combined with manual chest compression is hemodynamically safe for stable septic-shocked subjects over the short-term.

Diretrizes para avaliação e validação do potencial doador de órgãos em morte encefálica / Guidelines for the assessment and acceptance of potential brain-dead organ donors

RESUMO O transplante de órgãos é a única alternativa para muitos pacientes portadores de algumas doenças terminais. Ao mesmo tempo, é preocupante a crescente desproporção entre a alta demanda por transplantes de órgãos e o baixo índice de transplantes efetivados. Dentre as diferentes causas que alimentam essa desproporção, estão os equívocos na identificação do potencial doador de órgãos e as contraindicações mal atribuídas pela equipe assistente. Assim, o presente documento pretende fornecer subsídios à equipe multiprofissional da terapia intensiva para o reconhecimento, a avaliação e a validação do potencial doador de órgãos.

ABSTRACT Organ transplantation is the only alternative for many patients with terminal diseases. The increasing disproportion between the high demand for organ transplants and the low rate of transplants actually performed is worrisome. Some of the causes of this disproportion are errors in the identification of potential organ donors and in the determination of contraindications by the attending staff. Therefore, the aim of the present document is to provide guidelines for intensive care multi-professional staffs for the recognition, assessment and acceptance of potential organ donors.

Fc Gamma Receptor IIA (CD32A) R131 Polymorphism as a Marker of Genetic Susceptibility to Sepsis.

Sepsis is a devastating disease that can affect humans at any time between neonates and the elderly and is associated with mortality rates that range from 30 to 80%. Despite intensive efforts, its treatment has remained the same over the last few decades. Fc receptors regulate multiple immune responses and have been investigated in diverse complex diseases. FcγRIIA (CD32A) is an immunoreceptor, tyrosine-based activation motif-bearing receptor that binds immunoglobulin G and C-reactive protein, important opsonins in host defense. We conducted a study of 702 patients (184 healthy individuals, 171 non-infected critically ill patients, and 347 sepsis patients) to investigate if genetic polymorphisms in the CD32A coding region affect the risk of septic shock. All individuals were genotyped for a variant at position 131 of the FcγRIIA gene. We found that allele G, associated with the R131 genotype, was significantly more frequent in septic patients than in the other groups (p = 0.05). Our data indicate that FcγRIIA genotyping can be used as a marker of genetic susceptibility to sepsis.

Effect of 593C>T GPx1 SNP alone and in synergy with 47C>T SOD2 SNP on the outcome of critically ill patients.

During critical illness and sepsis there is severe antioxidant depletion, and this scenario raises the critical ill patient's mortality risk. Glutathione peroxidase (GPx) is one of the first endogenous antioxidant defense enzymes, and it works cooperatively with superoxide dismutase (SOD) and catalase (CAT) to detoxify free radicals from the cellular environment. Genetic studies are important to understand the complexity of human oxidative stress and how the organism responds to an extreme situation such as critically care conditions. Previous studies with a GPx1 single nucleotide polymorphism (593C>T SNP; rs1050450; protein variant in GPx1: Pro198Leu) showed 593T carriers and 593TT homozygotes present higher risk to develop different diseases. We assessed the relationship of the genotype distribution of GPx1 SNP in critically ill patients with their conditions (organ dysfunction, sepsis, and septic shock) and their outcome. We monitored 626 critically ill patients daily from the ICU (intensive care unit) admission to their discharge from hospital, or death. Our study revealed a significant association between 593TT GPx1 genotype and mortality; the mortality rate was higher in homozygous 593TT GPx1 (N=94) when compared with the group of subjects with genotypes 593CT or 593CC GPx1 (N=532) (52% vs. 38%, P=0.009; OR=1.79; 95% CI=1.13-2.85). Evaluating the subgroup of 293 ICU patients with sepsis, a pooled analysis including two genetic variants GPx1 and SOD2 (47C>T SNP, rs4880; protein variant in MnSOD: Ala-9Val) showed a significant difference in relation to progression to septic shock. The frequency of septic shock among septic patients with 593T GPx1 and 47C SOD2 alleles (N=122) was higher when compared with septic patients carrying other settings of genotypes (N=174) (78% vs. 66%; P=0.028; OR=1.81; 95% CI=1.03-3.18). Accepting the previously reported functional effects of these two SNPs on GPx1 and SOD2 gene expressions and, consequently, on GPx1 and MnSOD enzyme activities, we believe our results may be considered as an important contribution for the understanding of oxidative imbalance during the critical ill.

Monitorização hemodinâmica em unidade de terapia intensiva: uma perspectiva do Brasil / Hemodynamic monitoring in the intensive care unit: a Brazilian perspective

Objetivo: No Brasil, não há dados sobre as preferências do intensivista em relação aos métodos de monitorização hemodinâmica. Este estudo procurou identificar os métodos utilizados por intensivistas nacionais, as variáveis hemodinâmicas por eles consideradas importantes, as diferenças regionais, as razões para escolha de um determinado método, o emprego de protocolos e treinamento continuado. Métodos: Intensivistas nacionais foram convidados a responder um questionário em formato eletrônico durante três eventos de medicina intensiva e, posteriormente, por meio do portal da Associação de Medicina Intensiva Brasileira, entre março e outubro de 2009. Foram pesquisados dados demográficos e aspectos relacionados às preferências do entrevistado em relação à monitorização hemodinâmica. Resultados: Responderam ao questionário 211 profissionais. Nos hospitais privados, foi evidenciada maior disponibilidade de recursos de monitorização hemodinâmica do que nas instituições públicas. O cateter de artéria pulmonar foi considerado o mais fidedigno por 56,9%, seguido do ecocardiograma, com 22,3%. O débito cardíaco foi considerado a variável mais importante. Outras variáveis também julgadas relevantes foram débito cardíaco, saturação de oxigênio venoso misto/saturação de oxigênio venoso central, pressão ...

Objective: In Brazil, there are no data on the preferences of intensivists regarding hemodynamic monitoring methods. The present study aimed to identify the methods used by national intensivists, the hemodynamic variables they consider important, the regional differences, the reasons for choosing a particular method, and the use of protocols and continued training. Methods: National intensivists were invited to answer an electronic questionnaire during three intensive care events and later, through the Associação de Medicina Intensiva Brasileira portal, between March and October 2009. Demographic data and aspects related to the respondent preferences regarding hemodynamic monitoring were researched. Results: In total, 211 professionals answered the questionnaire. Private hospitals showed higher availability of resources for hemodynamic monitoring than did public institutions. The pulmonary artery catheter was considered the most trusted by 56.9% of the respondents, followed by echocardiograms, at 22.3%. Cardiac output was considered the most important variable. Other variables also considered relevant were mixed/central venous oxygen saturation, pulmonary artery occlusion pressure, and right ventricular end-diastolic volume. Echocardiography was the most used method (64.5%), followed by pulmonary artery catheter (49.3%). Only half of respondents used treatment protocols, and 25% worked in continuing education programs in hemodynamic monitoring. ...

Hemodynamic monitoring in the intensive care unit: a Brazilian perspective.

OBJECTIVE: In Brazil, there are no data on the preferences of intensivists regarding hemodynamic monitoring methods. The present study aimed to identify the methods used by national intensivists, the hemodynamic variables they consider important, the regional differences, the reasons for choosing a particular method, and the use of protocols and continued training. METHODS: National intensivists were invited to answer an electronic questionnaire during three intensive care events and later, through the Associação de Medicina Intensiva Brasileira portal, between March and October 2009. Demographic data and aspects related to the respondent preferences regarding hemodynamic monitoring were researched. RESULTS: In total, 211 professionals answered the questionnaire. Private hospitals showed higher availability of resources for hemodynamic monitoring than did public institutions. The pulmonary artery catheter was considered the most trusted by 56.9% of the respondents, followed by echocardiograms, at 22.3%. Cardiac output was considered the most important variable. Other variables also considered relevant were mixed/central venous oxygen saturation, pulmonary artery occlusion pressure, and right ventricular end-diastolic volume. Echocardiography was the most used method (64.5%), followed by pulmonary artery catheter (49.3%). Only half of respondents used treatment protocols, and 25% worked in continuing education programs in hemodynamic monitoring. CONCLUSION: Hemodynamic monitoring has a greater availability in intensive care units of private institutions in Brazil. Echocardiography was the most used monitoring method, but the pulmonary artery catheter remains the most reliable. The implementation of treatment protocols and continuing education programs in hemodynamic monitoring in Brazil is still insufficient.

Spontaneous acute subdural hematoma and intracerebral hemorrhage in a patient with thrombotic microangiopathy during pregnancy.

Preeclampsia, HELLP syndrome (hemolysis, elevated liver enzymes, and low-platelet count), and acute fatty liver of pregnancy are the main causes of thrombotic microangiopathy and evere liver dysfunction during pregnancy and represent different manifestations of the same pathological continuum. The case of a 35-week pregnant woman who was admitted to an intensive care unit immediately after a Cesarean section due to fetal death and the presence of nausea, vomiting, and jaundice is reported. Postpartum preeclampsia and acute fatty liver of pregnancy were diagnosed. The patient developed an acute subdural hematoma and an intracerebral hemorrhage, which were subjected to neurosurgical treatment. The patient died from refractory hemolytic anemia and spontaneous bleeding of multiple organs. Preeclampsia HELLP syndrome, and acute fatty liver of pregnancy might overlap and be associated with potentially fatal complications, including intracranial hemorrhage, as in the present case. Early detection and diagnosis are crucial to ensure management and treatment success.

Hematoma subdural agudo espontâneo e hemorragia intracerebral em paciente com microangiopatia trombótica gestacional / Spontaneous acute subdural hematoma and intracerebral hemorrhage in a patient with thrombotic microangiopathy during pregnancy

Pré-eclâmpsia, síndrome HELLP (hemólise, elevação de enzimas hepáticas e plaquetopenia) e fígado gorduroso agudo da gestação são as principais causas de microangiopatia trombótica e disfunção hepática grave durante a gestação, representando um spectrum do mesmo processo patológico. Relatou-se aqui o caso de uma gestante com 35 semanas internada em unidade de terapia intensiva no pós-operatório imediato de cesariana por morte fetal, com náuseas, vômitos e icterícia. Diagnosticaram-se pré-eclâmpsia pós-parto e fígado gorduroso agudo da gestação. Houve evolução tardia com hematoma subdural agudo e hemorragia intracerebral, sendo realizado tratamento neurocirúrgico. A paciente foi a óbito por anemia hemolítica refratária, com sangramento espontâneo em múltiplos órgãos. Pré-eclâmpsia, síndrome HELLP e fígado gorduroso agudo da gestação são processos patológicos que podem se sobrepor e se associar a complicações potencialmente fatais, como a hemorragia intracraniana aqui descrita. Sua detecção e diagnóstico precoces são fundamentais para a instituição de manejo adequado e sucesso do tratamento.

Preeclampsia, HELLP syndrome (hemolysis, elevated liver enzymes, and low-platelet count), and acute fatty liver of pregnancy are the main causes of thrombotic microangiopathy and evere liver dysfunction during pregnancy and represent different manifestations of the same pathological continuum. The case of a 35-week pregnant woman who was admitted to an intensive care unit immediately after a Cesarean section due to fetal death and the presence of nausea, vomiting, and jaundice is reported. Postpartum preeclampsia and acute fatty liver of pregnancy were diagnosed. The patient developed an acute subdural hematoma and an intracerebral hemorrhage, which were subjected to neurosurgical treatment. The patient died from refractory hemolytic anemia and spontaneous bleeding of multiple organs. Preeclampsia HELLP syndrome, and acute fatty liver of pregnancy might overlap and be associated with potentially fatal complications, including intracranial hemorrhage, as in the present case. Early detection and diagnosis are crucial to ensure management and treatment success.

Higher frequency of septic shock in septic patients with the 47C allele (rs4880) of the SOD2 gene.

AIM: To analyze the effect of the two different versions of the manganese superoxide dismutase gene (SOD2) on sepsis. The SOD2 gene presents the 47C>T single nucleotide polymorphism (SNP; ID: rs4880) which produces MnSOD with different activities. The -9Val MnSOD (47T allele) is less efficient than the -9Ala version (47C allele). During sepsis there are abundance of ROS, high SOD2 expression and excess of H(2)O(2) synthesis. High concentrations of H(2)O(2) could affect the sepsis scenario and/or the sepsis outcome. METHODS: We determined the 47C>T single nucleotide polymorphism (SNP) frequencies in 529 critically ill patients with or without sepsis, facing outcome. To collect information on population frequencies, we obtained a pilot 47C>T genotypic and allelic frequencies in a random group of 139 healthy subjects. RESULTS: We compared the 47C allele carriers (47CC+47CT genotypes) with 47TT homozygotes and noticed a significant association between 47C allele carriers and septic shock in septic patients (P=0.025). With an adjusted binary multivariate logistic regression, incorporating 47C>T SNP and the main clinical predictors, we showed high SOFA scores [P<0.001, OR=9.107 (95% CI=5.319-15.592)] and 47C allele [P=0.011, OR=2.125 (95% CI=1.190-3.794)] were significantly associated with septic shock outcome. With this information we presented a hypothesis suggesting that this negative outcome from sepsis is possibly explained by effects on cellular stress caused by 47C allele. CONCLUSION: In our population there was a significant higher frequency of septic shock in septic patients with the 47C allele of the SOD2 gene. This higher 47C allele frequency in septic patients with negative outcome could be explained by effects of higher activity MnSOD on cellular stress during the sepsis.

Diretrizes para manutenção de múltiplos órgãos no potencial doador adulto falecido: Parte III. Recomendações órgãos específicas / Guidelines for potential multiple organ donors (adult). Part III: organ-specific recommendations

A morte encefálica induz várias alterações fisiopatológicas que podem causar lesões em rins, pulmões, coração e fígado. Portanto, a atuação do intensivista durante a manutenção do potencial doador falecido exige cuidados específicos com estes órgãos visando sua maior viabilidade para transplantes. O manejo hemodinâmico cuidadoso, os cuidados ventilatórios e de higiene brônquica minimizam a perda de rins e pulmões para o transplante. A avaliação da condição morfológica e funcional do coração auxilia na avaliação do potencial transplantável deste órgão. Por fim, a avaliação da função hepática, assim como o controle metabólico e a realização de sorologias virais são fundamentais para a orientação das equipes transplantadoras na seleção do órgão a ser doado e no cuidado com o receptor.

Brain death (BD) alters the pathophysiology of patients and may damage the kidneys, the lungs, the heart and the liver. To obtain better quality transplant organs, intensive care physicians in charge of the maintenance of deceased donors should attentively monitor these organs. Careful hemodynamic, ventilatory and bronchial clearance management minimizes the loss of kidneys and lungs. The evaluation of cardiac function and morphology supports the transplant viability assessment of the heart. The monitoring of liver function, the management of the patient's metabolic status and the evaluation of viral serology are fundamental for organ selection by the transplant teams and for the care of the transplant recipient.

Guidelines for potential multiple organ donors (adult). Part III: organ-specific recommendations. / Diretrizes para manutenção de múltiplos órgãos no potencial doador adulto falecido: Parte III. Recomendações órgãos específicas.

Brain death (BD) alters the pathophysiology of patients and may damage the kidneys, the lungs, the heart and the liver. To obtain better quality transplant organs, intensive care physicians in charge of the maintenance of deceased donors should attentively monitor these organs. Careful hemodynamic, ventilatory and bronchial clearance management minimizes the loss of kidneys and lungs. The evaluation of cardiac function and morphology supports the transplant viability assessment of the heart. The monitoring of liver function, the management of the patient's metabolic status and the evaluation of viral serology are fundamental for organ selection by the transplant teams and for the care of the transplant recipient.

Temporal trends in acute renal dysfunction among critically ill patients according to I/D and -262A > T ACE polymorphisms.

Multiple organ failure syndrome and acute renal dysfunction share many of physiologic factors involved in their development. Recent studies correlate the susceptibility to organ dysfunction in critically ill patients with genetic inheritance. Many of them consider ACE gene could be a possible candidate to elucidate a genetic predisposition or a genetic risk factor. We aimed to examine the effects of I/D and -262A > T ACE polymorphisms in the renal function in severely ill southern Brazilians patients. A multi-organic worldwide known failure score, the SOFA (sequential organ failure assessment), was used to determine the basal health state at first day (ICU admission). Considering admission SOFA score and trend of renal function (measured by daily renal SOFA scores, with daily measure of serum creatinine and diuresis), we hypothesize that ACE polymorphisms could influence in the trend of renal function in ICU patients. A total of 153 critically ill adult patients (79 men) were included in this study. We monitored the patients daily during their entire ICU and post-ICU (hospital) stay (measured from the ICU admission day to a maximum of 224 days). We observed progression to renal failure (SOFA scores 3 and 4) in first seven days of ICU stay and need for dialysis. The general genotypic frequencies in our sample were II = 0.17; ID = 0.46; DD = 0.37 and AA = 0.30; AT = 0.55; TT = 0.15, and the allelic frequencies were I = 0.40; D = 0.60 and A = 0.56; T = 0.44. This is the first study to verify the influence of I/D and -262A > T ACE polymorphisms in acute renal dysfunction among critically ill patients. No significant association was found between genotypes or allele frequencies and the trend of the renal function. The I/D and -262A > T ACE polymorphisms have no significant impact on the trend of renal function during the first week of ICU stay, neither any influence in mortality in critically ill patients.

Very low frequencies of Toll-like receptor 2 supposed-2029T and 2258A (RS5743708) mutant alleles in southern Brazilian critically ill patients: would it be a lack of worldwide-accepted clinical applications of Toll-like receptor 2 variants?

Toll-like receptor 2 (TLR2) is a recognition receptor for the widest repertoire of pathogen-associated molecular patterns. Two polymorphisms of TLR2 could be linked to reduced nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) activation and to increased risk of infection (supposed-2029C>T and 2258G>A). We investigated the supposed-2029C>T and 2258G>A TLR2 polymorphisms in 422 critically ill patients of European origin from southern Brazil (295 with sepsis and 127 without sepsis) and reviewed 33 studies on these polymorphisms, conducting a quality assessment with a score system. Among our patients we found only one heterozygote (1/422) for the supposed-2029C>T and none for the 2258G>A (0/422) single nucleotide polymorphism (SNP). We were unable to find a clinical application of supposed-2029T and 2258A allele analyses in our southern Brazilian population. Our review detected that current TLR2 SNP assays had very controversial and contradictory results derived from reports with a variety of investigation quality criteria. We suggest that, if analyzed alone, the supposed-2029C>T and 2258G>A TLR2 SNP are not good candidates for genetic markers in studies that search for direct or indirect clinical applications between genotype and phenotype. Future efforts to improve the knowledge and to provide other simultaneous genetic markers might reveal a more effective TLR2 effect on the susceptibility to infectious diseases.