Fernando Suparregui Dias

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 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.

CD14 expression in the first 24h of sepsis: effect of -260C>T CD14 SNP.

Sepsis is defined as systemic inflammation caused by infection. The membrane bound CD14 (mCD14) or the soluble form (sCD14) play a crucial role facing Gram-negative and Gram-positive sepsis since they are pattern recognition receptors of the innate immune response enabling cells to produce inflammatory cytokines against bacterial infections. A −260C>T single nucleotide polymorphism (SNP) was detected in the promoter modulating the CD14 gene expression. We hypothesized that the CD14 expression depends of the genetic inheritance of −260C>T CD14 SNP and it is modulated by sepsis condition. We investigated human CD14 expression on early sepsis diagnosis (in vivo) and after LPS stimulation (in vitro), and determined the −260C>T CD14 SNP. We found that TT homozygotes showed higher mCD14 density (p = 0.0207), but not different sCD14 levels when compared to the CT+CC genotypes. Monocyte mCD14 density and sCD14 serum levels in our sample of early 14 septic patients were significantly higher than normal 30 controls (p<0.0001). Our results suggest that the −260TT CD14 genotype is associated with higher monocyte mCD14, but not sCD14 expression, and that in the first 24 h after sepsis diagnosis, both monocyte mCD14 density and sCD14 levels are elevated, similarly to what is observed in vitro upon challenge with LPS.

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 (κ=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, χ2 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.

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.

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) patients 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.

Diretrizes para avaliação e validação do potencial doador de órgãos em morte encefálica

O transplante de orgaos e a unica alternativa para muitos pacientes portadores de algumas doencas terminais. Ao mesmo tempo, e preocupante a crescente desproporcao entre a alta demanda por transplantes de orgaos e o baixo indice de transplantes efetivados. Dentre as diferentes causas que alimentam essa desproporcao, estao os equivocos na identificacao do potencial doador de orgaos e as contraindicacoes mal atribuidas pela equipe assistente. Assim, o presente documento pretende fornecer subsidios a equipe multiprofissional da terapia intensiva para o reconhecimento, a avaliacao e a validacao do potencial doador de orgaos.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.

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.

Optimizing perioperative hemodynamics: what is new?

Purpose of reviewUsing 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 findingsOne 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. SummaryGDT 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.

Análise da tendência temporal de dano renal agudo entre pacientes graves conforme polimorfi smos I/D e -262A > T da enzima conversora da angiotensina

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.