Reduced frequency of two activating KIR genes in patients with sepsis.

Natural killer (NK) cell activity is regulated by activating and inhibitory signals transduced by killer cell immunoglobulin-like receptors (KIR). Diversity in KIR gene repertoire among individuals may affect disease outcome. Sepsis development and severity may be influenced by genetic factors affecting the immune response. Here, we examined sixteen KIR genes and their human leucocyte antigen (HLA) class I ligands in critical patients, aiming to identify patterns that could be associated with sepsis. Male and female patients (ages ranging between 14 and 94years-old) were included. DNA samples from 211 patients with sepsis and 60 controls (critical care patients with no sepsis) collected between 2004 and 2010 were included and genotyped for KIR genes using the polymerase chain reaction method with sequence-specific oligonucleotide (PCR-SSO), and for HLA genes using the polymerase chain reaction method with sequence-specific primers (PCR-SSP). The frequencies of activating KIR2DS1 and KIR3DS1 in sepsis patients when compared to controls were 41.23% versus 55.00% and 36.49% versus 51.67% (p=0.077 and 0.037 respectively before Bonferroni correction). These results indicate that activating KIR genes 2DS1 and 3DS1 may more prevalent in critical patients without sepsis than in patients with sepsis, suggesting a potential protective role of activating KIR genes in sepsis.

Immediate effects of chest physiotherapy on hemodynamic, metabolic, and oxidative stress parameters in subjects with septic shock.

BACKGROUND: Septic shock presents as a continuum of infectious events, generating tissue hypoxia and hypovolemia, and increased oxidative stress. Chest physiotherapy helps reduce secretion, improving dynamic and static compliance, as well as improving secretion clearance and preventing pulmonary complications. The purpose of this study was to evaluate the immediate effect of chest physiotherapy on hemodynamic, metabolic, inflammatory, and oxidative stress parameters in subjects in septic shock. METHODS: We conducted a quasi-experimental study in 30 subjects in septic shock, who underwent chest physiotherapy, without associated heart diseases and with vasopressors < 0.5 µg/kg/min. Venous and arterial blood gases, clinical and hemodynamic data, inflammatory data, lactate, and oxidative stress were evaluated before and 15 min after physiotherapy. RESULTS: Thirty subjects with a mean age of 61.8 ± 15.9 y and Sequential Organ Failure Assessment of 8 (range 6-10) were included. Chest physiotherapy caused a normalization of pH (P = .046) and P(aCO2) (P = .008); reduction of lactate (P = .001); and an increase in P(aO2) (P = .03), arterial oxygen saturation (P = .02), and P(aO2)/F(IO2) (P = .034), 15 min after it was applied. CONCLUSIONS: The results indicate that chest physiotherapy has immediate effects, improving oxygenation and reducing lactate and oxidative damage in subjects in septic shock. However, it does not cause alterations in the inflammatory and hemodynamic parameters.

Optimizing perioperative hemodynamics: what is new?

PURPOSE OF REVIEW: Using perioperative goal-directed therapy (GDT) or peroperative hemodynamic optimization significantly reduces postoperative complications and risk of death in patients undergoing noncardiac major surgeries. In this review, we discuss the main changes in the field of perioperative optimization over the last few years. RECENT FINDINGS: One of the key aspects that has changed in the last decade is the shift from invasive monitoring with pulmonary artery catheters (PACs) to less or minimally invasive monitoring systems. The evaluation of intravascular fluid volume deficits has also changed dramatically from the use of static indices to the assessment of fluid responsiveness using either dynamic indices or functional hemodynamic. Finally, attention has been directed toward more restrictive strategies of crystalloids as maintenance fluids. SUMMARY: GDT is safe and more likely to tailor the amount of fluids given to the amount of fluids actually needed. This approach includes assessment of fluid responsiveness and, if necessary, the use of inotropes; moreover, this approach can be coupled with a restrictive strategy for maintenance fluids. These strategies have been increasingly incorporated into protocols for perioperative hemodynamic optimization in high-risk patients undergoing major surgery, resulting in more appropriate use of fluids, vasopressors, and inotropes.

Polymorphic variants in exon 8 at the 3' UTR of the HLA-G gene are associated with septic shock in critically ill patients.

INTRODUCTION: Critically ill patients are characterized as individuals hospitalized in the Intensive Care Unit (ICU) and can evolve to sepsis, septic shock or even death. Among others, genetic factors can influence the outcome of critically ill patients. HLA-G is a non-classical class Ib molecule that has limited protein variability, presenting seven isoforms generated by alternative splicing, and presents immunomodulatory properties. Polymorphisms at the 3'UTR are thought to influence HLA-G gene expression. It was previously observed that increased sHLA-G5 levels were predictive of survival among septic shock patients. We assessed the frequencies of 7 polymorphisms in exon 8 at the 3' UTR of HLA-G and associated these variants with different clinical outcomes in critically ill patients. METHODS: Exon 8 at the 3' UTR of the HLA-G gene from 638 critically ill subjects was amplified by PCR and sequenced. Genotypes were identified using FinchTV software v.1.4.0 and the most probable haplotype constitution of each sample was determined by PHASE software v.2.1. Haplotype frequencies, linkage disequilibrium, heterozygosity test and Hardy-Weinberg Equilibrium were estimated using ARLEQUIN software v.3.5. RESULTS: Among all critically ill patients, an association between carriers of the +2960IN_+3142 G_+3187A haplotype and septic shock (P = 0.047) was observed. Septic patients who carried the +2960IN_+3142G_+3187A haplotype presented an increased risk for septic shock (P = 0.031). CONCLUSIONS: The present study showed, for the first time, an association between polymorphisms in exon 8 at the 3 'UTR of HLA-G gene and outcomes of critically ill patients. These results may be important for understanding the mechanisms involved in evolution to septic shock in critically ill patients.

TNF -308G > a promoter polymorphism (rs1800629) and outcome from critical illness.

BACKGROUND: The susceptibility to adverse outcome from critical illness (occurrence of sepsis, septic shock, organ dysfunction/failure, and mortality) varies dramatically due to different degrees of inflammatory response. An over expression of tumor necrosis factor alpha (TNF-α) can lead to the progression of the inflammatory condition. OBJECTIVE: We assessed the relationship of the genotype distribution of -308G >A TNF-α polymorphism with regard to the development of sepsis, septic shock, higher organ dysfunction or mortality in critically ill patients. METHODS: Observational, hospital-based cohort study of 520 critically ill Caucasian patients from southern Brazil admitted to the general ICU of São Lucas Hospital, Porto Alegre, Brazil. Patients were monitored daily from the ICU admission day to hospital discharge or death, measuring SOFA score, sepsis, and septic shock occurrences. The -308G >A TNF-α SNP effect was analyzed in the entire patient group, in patients with sepsis (349/520), and in those who developed septic shock (248/520). RESULTS: The genotypic and allelic frequencies were -308GG = 0.72; -308GA = 0.27; -308AA = 0.01; -308G = 0.85; -308A = 0.15. No associations were found with sepsis, septic shock, organ dysfunction, and/or mortality rates among the TNF-α genotypes. Our results reveal that the -308G >A TNF-α SNP alone was not predictive of severe outcomes in critically ill patients. CONCLUSION: The principal novel input of this study was the larger sample size in an investigation with -308G > A TNF-α SNP. The presence of -308A allele is not associated with sepsis, septic shock, higher organ dysfunction or mortality in critically ill patients.

TNF -308G > a promoter polymorphism (rs1800629) and outcome from critical illness

BACKGROUND: The susceptibility to adverse outcome from critical illness (occurrence of sepsis, septic shock, organ dysfunction/failure, and mortality) varies dramatically due to different degrees of inflammatory response. An over expression of tumor necrosis factor alpha (TNF-α) can lead to the progression of the inflammatory condition. OBJECTIVE: We assessed the relationship of the genotype distribution of -308G >A TNF-α polymorphism with regard to the development of sepsis, septic shock, higher organ dysfunction or mortality in critically ill patients. METHODS: Observational, hospital-based cohort study of 520 critically ill Caucasian patients from southern Brazil admitted to the general ICU of São Lucas Hospital, Porto Alegre, Brazil. Patients were monitored daily from the ICU admission day to hospital discharge or death, measuring SOFA score, sepsis, and septic shock occurrences. The -308G >A TNF-α SNP effect was analyzed in the entire patient group, in patients with sepsis (349/520), and in those who developed septic shock (248/520). RESULTS: The genotypic and allelic frequencies were -308GG = 0.72; -308GA = 0.27; -308AA = 0.01; -308G = 0.85; -308A = 0.15. No associations were found with sepsis, septic shock, organ dysfunction, and/or mortality rates among the TNF-α genotypes. Our results reveal that the -308G >A TNF-α SNP alone was not predictive of severe outcomes in critically ill patients. CONCLUSION: The principal novel input of this study was the larger sample size in an investigation with -308G > A TNF-α SNP. The presence of -308A allele is not associated with sepsis, septic shock, higher organ dysfunction or mortality in critically ill patients.

Evaluating end of life practices in ten Brazilian paediatric and adult intensive care units.

OBJECTIVE: To evaluate the modes of death and treatment offered in the last 24 h of life to patients dying in 10 Brazilian intensive care units (ICUs) over a period of 2 years. DESIGN AND SETTING: Cross-sectional, multicentre, retrospective study based on medical chart review. The medical records of all patients that died in seven paediatric and three adult ICUs belonging to university and tertiary hospitals over a period of 2 years were included. Deaths in the first 24 h of admission to the ICU and brain death were excluded. INTERVENTION: Two intensive care fellows of each ICU were trained in fulfilling a standard protocol (kappa=0.9) to record demographic data and all medical management provided in the last 48 h of life. The Student t test, Mann-Whitney U test, chi(2) test and RR were used for data comparison. MEASUREMENTS AND MAIN RESULTS: 1053 medical charts were included (59.4% adult patients). Life support limitation was more frequent in the adult group (86% vs 43.5%; p<0.001). A 'do not resuscitate' order was the most common life support limitation in both groups (75% and 66%), whereas withholding/withdrawing were more frequent in the paediatric group (33.9% vs 24.9%; p=0.02). The life support limitation was rarely reported in the medical chart in both groups (52.6% and 33.7%) with scarce family involvement in the decision making process (23.0% vs 8.7%; p<0.001). CONCLUSION: Life support limitation decision making in Brazilian ICUs is predominantly centred on the medical perspective with scarce participation of the family, and consequently several non-coherent medical interventions are observed in patients with life support limitation.

The influences of CD14 -260C>T polymorphism on survival in ICU critically ill patients.

In order to analyze the effect of the two different versions of the cluster of differentiation 14 (CD14) receptor recognizing gene on survival, we determined the -260C>T single nucleotide polymorphism (SNP) frequencies in 514 critically ill patients. We compared the -260TT homozygotes with -260C allele carriers (-260CC and -260CT genotypes) and we demonstrated--260TT patients had the highest survival rate (82% vs 64%; p < 0.001; OR = 2.52, 95% CI = 1.43-4.46). We performed binary logistic regression, incorporating both -260C>T genotype groups and the main clinical predictors to exclude other risk factors that could influence the outcome from critical illness: higher age, APACHE II score, and length of stay at hospital, and the occurrence of sepsis and septic shock were risk factors to Intensive Care Unit (ICU) patient's mortality, but the -260TT genotype was protective factor toward survival (p = 0.001; OR = 3.08 95%CI = 1.54-5.98). Among septic and septic shock patients, -260TT genotype was also protective factor toward survival (p = 0.001; OR = 3.11 95%CI = 1.63-6.66 to septic patients, and p = 0.001; OR = 3.80 95%CI = 1.68-8.58 to patients with septic shock). Our results and our hypothesis suggest that the higher -260TT genotype frequency in ICU survivor patients is possibly explained by a beneficial effect on innate immunity signaling.

Prevalência de infecção nosocomial em Unidades de Terapia Intensiva do Rio Grande do Sul / The prevalence of nosocomial infection in Intensive Care Units in the State of Rio Grande do Sul

JUSTIFICATIVA E OBJETIVOS: Determinar a prevalência de infecções adquiridas em UTI e os fatores de risco para estas infecções, identificar os organismos infectantes mais prevalentes, avaliar a relação entre infecção adquirida na UTI e mortalidade. MÉTODO: Estudo de prevalência de um dia. Participaram do estudo 16 UTI do estado do Rio Grande do Sul, excluindo unidades coronarianas ou pediátricas. Todos os pacientes com idade maior que 12 anos, ocupando um leito de UTI por um período de 24h, foram incluídos. As 16 UTI coletaram dados de 174 pacientes. Principais desfechos: taxas de infecção adquirida na UTI, padrões de resistência dos patógenos isolados e fatores potenciais de risco para infecção adquirida na UTI e mortalidade. RESULTADOS: Um total de 122 pacientes (71 por cento) estava infectado, e 51 (29 por cento) adquiriram infecção na UTI. Pneumonia (58,2 por cento), infecção do trato respiratório inferior (22,9 por cento), infecção do trato urinário (18 por cento) foram os tipos mais freqüentes de infecção. Os microorganismos mais relatados foram stafilococos aureus (42 por cento [64 por cento resistentes a oxacilina]) e pseudomonas aeruginosa (31 por cento). Seis fatores de risco foram identificados para infecção adquirida na UTI: cateter urinário, acesso vascular central, intubação traqueal por tempo prolongado (> 4 dias), doença crônica, trauma e internação prolongada na UTI (> 30 dias). Os fatores de risco associados à morte foram idade, APACHE II, falência orgânica e prótese em via aérea com ou sem ventilação mecânica. CONCLUSÕES: A infecção adquirida na UTI é comum e freqüentemente associada a isolados de microorganismos resistentes. Este estudo, apesar de sua abrangência regional, serve de referência epidemiológica para ajudar a programar políticas de controle de infecção.

BACKGROUND AND OBJECTIVES: To determine the prevalence of intensive care unit (ICU)-acquired infections and the risk factors for these infections, identify the predominant infecting organisms, and evaluate the relationship between ICU-acquired infection and mortality. METHODS: A 1-day point prevalence study. Sixteen ICU of the State of Rio Grande do Sul-Brazil, excluding coronary care and pediatric units. All patients < 12 yrs occupying an ICU bed over a 24-hour period. The 16 ICU provided 174 case reports. Main outcomes: rates of ICU-acquired infection, resistance patterns of microbiological isolates, and potential risks factors for ICU-acquired infection and death. RESULTS: A total of 122 patients (71 percent) was infected and 51 (29 percent) had ICU-acquired infection. Pneumonia (58.2 percent), lower tract respiratory infection (22.9 percent), urinary tract infection (18 percent) were the most frequents types of ICU infection. Most frequently microorganisms reported were staphylococcus aureus (42 percent [64 percent resistant to oxacilin]) and pseudomonas aeruginosa (31 percent). Six risk factors for ICU acquired infection were identified: urinary catheterization, central vascular line, tracheal intubation for prolonged time (> 4 days), chronic disease and increased length of ICU stay (> 30 days). The risks factors associated with death were age, APACHE II, organ dysfunction, and tracheal intubation with or without mechanical ventilation. CONCLUSIONS: ICU-acquired infection is common and often associated with microbiological isolates of resistant organisms. This study may serve as an epidemiological reference to help the discussion of regional infection control policies.

[The prevalence of nosocomial infection in Intensive Care Units in the State of Rio Grande do Sul]. / Prevalência de infecção nosocomial em Unidades de Terapia Intensiva do Rio Grande do Sul.

BACKGROUND AND OBJECTIVES: To determine the prevalence of intensive care unit (ICU)-acquired infections and the risk factors for these infections, identify the predominant infecting organisms, and evaluate the relationship between ICU-acquired infection and mortality. METHODS: A 1-day point prevalence study. Sixteen ICU of the State of Rio Grande do Sul-Brazil, excluding coronary care and pediatric units. All patients < 12 yrs occupying an ICU bed over a 24-hour period. The 16 ICU provided 174 case reports. MAIN OUTCOMES: rates of ICU-acquired infection, resistance patterns of microbiological isolates, and potential risks factors for ICU-acquired infection and death. RESULTS: A total of 122 patients (71%) was infected and 51 (29%) had ICU-acquired infection. Pneumonia (58.2%), lower tract respiratory infection (22.9%), urinary tract infection (18%) were the most frequents types of ICU infection. Most frequently microorganisms reported were staphylococcus aureus (42% [64% resistant to oxacilin]) and pseudomonas aeruginosa (31%). Six risk factors for ICU acquired infection were identified: urinary catheterization, central vascular line, tracheal intubation for prolonged time (> 4 days), chronic disease and increased length of ICU stay (> 30 days). The risks factors associated with death were age, APACHE II, organ dysfunction, and tracheal intubation with or without mechanical ventilation. CONCLUSIONS: ICU-acquired infection is common and often associated with microbiological isolates of resistant organisms. This study may serve as an epidemiological reference to help the discussion of regional infection control policies.

Effect of CD14 -260C>T polymorphism on the mortality of critically ill patients.

The CD14 receptor seems to be an important part of the innate immune system. A mutant CD14 can produce a reduced signal in response to infection, as a result of which an adequate inflammatory innate response is not induced, leading to a systemic infection. Defects in the innate immunity increase patient susceptibility to systemic infections and can produce a deregulated inflammatory response causing sepsis, organ failure or death in critically ill patients. We evaluated the CD14 -260C>T polymorphism genotyping as a genetic tool for risk evaluation of critically ill patients admitted to an intensive care unit (ICU) in Southern Brazil. 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). A total of 85 patients, aged 19-95 years (mean = 56 years, median = 58 years), were included in this study. Patient mortality was 58.8%. The genotypic (TT = 0.27, TC = 0.41, CC = 0.32) and allelic (T = 0.48, C = 0.52) frequencies did not differ from the values expected by the Hardy-Weinberg model and genotype distribution was random for all clinical characteristics at ICU admission. We found a statistically significant difference favouring the survival of patients with TT genotype (P = 0.042), suggesting that this CD14 gene polymorphism could be a candidate for further study in the search for a complementary prognostic tool for patient risk evaluation. Our study describes, for the first time, the effect of the CD14 gene polymorphism in critically ill Brazilian patients. Our data suggest that patients carrying the TT genotype have a better survival outcome.

Efeito da frutose-1, 6bisfosfato sobre os níveis séricos e urinários de lactato em ratos com sepse experimental / Effect of fructose-1, 6-bisphosphate on serum and urine levels of lactate in rats with experimental sepsis

As alterções celulares e sistêmicas durante a sepse ocasionam distúrbios na circulação, queda na perfuração tecidual e consequentemente déficit de energia celular. A frutose-1-6-bisfosfato (FBP) tem demonstrado efeitos protetores em diversas situações patológicas, inclusive sepse. O objetivo deste travalho foi verificar a concentração de FBP em animais com sepse experimental. Estudo controlado em ratos Wistar divididos em 4 grupos: grupo controle com FBP(500 mg/kg). A concentração sérica de lactato aumentou signitivamente no grupo séptico. Analisando a depuração de creatinina endógena(DCE) verificou-se, que somente o grupo séptico apresentou uma diminuição significativa. Já o lactato urinário não demonstrou alterações entre os grupos de controle, séptico e séptico tratado, aumentando, porém significativamente no grupo co FBP. Este estudo demonstrou que o lactato urinário é bom marcador de perfusão tecidual na spse. Também pôde-se verificar que a ação protetora da FBP não é por melhora da perfusão tecidual, mas provavelmente por outros efeitos já descritos, tais como, ação antiflamatória, manutenção dos níveis de energia da célula, estabilização da membrana celular.

Avaliaçäo da mortalidade em uma UTI Geral através do escore APACHE II: análise de 1411 casos consecutivos / Evaluation of mortality in a General ICU using APACHE II score: analysis of 1411 consecutive patients

Com o objetivo de avaliar a mortalidade em uma unidade de terapia intensiva geral através do escore Acute Physiology, Age, Chronic Health Evaluation (APACHE II), foi feito estudo observacional retrospectivo, com pacientes internados entre janeiro de 1997 e dezembro de 19999 na UTI geral do HSL-PUCRS