Genetic polymorphisms of innate and adaptive immunity as predictors of outcome in critically ill patients.

Sepsis and septic shock frequently cause the admission or complicate the clinical course of critically ill patients admitted in the intensive care units (ICU). Genetic variations disrupting the immune sensing of infectious organisms, could affect the ability of the immune system to respond to infection, and may influence both the genetic predisposition to infection and the diversity of the clinical presentation of sepsis. The aim of this study was to uncover possible associations between common functional immune gene polymorphisms (of both innate and adaptive immunity) and ICU-acquired sepsis and mortality. The TLR4-D299G (rs4986790), TLR4-T399I (rs4986791), C2-c.841_849+19del28 (rs9332736), TACI-C104R (rs34557412), BAFFR-P21R (rs77874543), and BAFFR-H159Y (rs61756766) polymorphisms were detected in a cohort of 215 critically ill patients, admitted in an 8-bed medical/surgical ICU. Interestingly, TLR4-D299G, TLR4-T399I and BAFFR-P21R carriage was associated with a lower risk of ICU-acquired sepsis. This association applied particularly in medical patients, while in trauma and surgical patients no significant associations were observed. Moreover, carriers of TACI-C104R displayed an undiagnosed mild to moderate hypogammaglobulinemia along with a significantly lower survival rate in the ICU, although lethal events were not attributed to sepsis. These findings further elucidate the role that host immune genetic variations may play in the susceptibility to ICU-acquired sepsis and ICU mortality.

Glycated hemoglobin at admission in the intensive care unit: clinical implications and prognostic relevance.

OBJECTIVE: This study investigated the clinical significance of HbA1c levels on admission in the intensive care unit (ICU) as a prognostic marker for morbidity and mortality in critically ill patients. PATIENTS-METHODS: This prospective observational study included consecutive patients admitted in an 8-bed multidisciplinary ICU. Patients were prospectively followed from ICU admission until ICU outcome (death/discharge). All patients had an HbA1c measurement upon admission in the ICU. RESULTS: Five hundred fifty-five consecutive patients (376 males, 179 females) were included in the study. In patients without prior diabetes mellitus (DM) diagnosis, a cutoff of 6.5% for HbA1c (diagnostic cutoff for DM) predicted more severe disease (as described by Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores at admission) and higher ICU mortality (adjusted odds ratio, 2.33; 95% confidence interval, 1.04-5.25). In the subgroup of patients with a history of DM, a cutoff of 7% for HbA1c (glycemic target) had no predicting ability for ICU mortality. CONCLUSIONS: HbA1c is a useful tool for the diagnosis of a previously undiagnosed DM. This study showed that in critically ill patients with previously undiagnosed DM, HbA1c at admission is significantly associated with ICU mortality.

Impact of red blood cells transfusion on ICU-acquired bloodstream infections: a case-control study.

Our study investigated the impact of packed red blood cell (pRBC) transfusion on the occurrence of bloodstream infections (BSIs) in patients admitted in a multidisciplinary intensive care unit (ICU), further assessing potential associations with particular BSI types. A nested matched (1:1) case-control design was implemented. Sex, age, admission category, Acute Physiology and Chronic Health Evaluation score II (plus Injury Severity Score in trauma patients) were used for matching. Controls were selected to have an ICU length of stay at least equal to the time to first BSI episode of the corresponding cases. Propensity scores for receiving pRBC transfusion were calculated in the entire prospective cohort. Of 582consecutive ICU patients, 165 matched case-control pairs were formed. In multivariable analysis, pRBC transfusion was independently associated with 2-fold probability for BSI (adjusting for matching variables and propensity score). There was a significant dose-dependent association of BSI risk with regard to the number of pRBC units transfused (odds ratios [OR], 1.73, 2.09, 2.34 for 1-3, 4-6, and more than 6 pRBC units transfused, respectively, compared with nontransfused patients, P values .116, .018, and .015, respectively). In subgroup analysis, catheter-related BSIs displayed the strongest association with pRBC transfusion (OR = 5.01, P = .014).

End-of-life decisions in Greek intensive care units: a multicenter cohort study.

INTRODUCTION: Intensive care may prolong the dying process in patients who have been unresponsive to the treatment already provided. Limitation of life-sustaining therapy, by either withholding or withdrawing support, is an ethically acceptable and common worldwide practice. The purpose of the present study was to examine the frequency, types, and rationale of limiting life support in Greek intensive care units (ICUs), the clinical and demographic parameters associated with it, and the participation of relatives in decision making. METHODS: This was a prospective observational study conducted in eight Greek multidisciplinary ICUs. We studied all consecutive ICU patients who died, excluding those who stayed in the ICU less than 48 hours or were brain dead. RESULTS: Three hundred six patients composed the study population, with a mean age of 64 years and a mean APACHE II score on admission of 21. Of study patients, 41% received full support, including unsuccessful cardiopulmonary resuscitation (CPR); 48% died after withholding of CPR; 8%, after withholding of other treatment modalities besides CPR; and 3%, after withdrawal of treatment. Patients in whom therapy was limited had a longer ICU (P < 0.01) and hospital (P = 0.01) length of stay, a lower Glasgow Coma Scale score (GCS) on admission (P < 0.01), a higher APACHE II score 24 hours before death (P < 0.01), and were more likely to be admitted with a neurologic diagnosis (P < 0.01). Patients who received full support were more likely to be admitted with either a cardiovascular (P = 0.02) or trauma diagnosis (P = 0.05) and to be surgical rather than medical (P = 0.05). The main factors that influenced the physician's decision were, when providing full support, reversibility of illness and prognostic uncertainty, whereas, when limiting therapy, unresponsiveness to treatment already offered, prognosis of underlying chronic disease, and prognosis of acute disorder. Relatives' participation in decision making occurred in 20% of cases and was more frequent when a decision to provide full support was made (P < 0.01). Advance directives were rare (1%). CONCLUSIONS: Limitation of life-sustaining treatment is a common phenomenon in the Greek ICUs studied. However, in a large majority of cases, it is equivalent to the withholding of CPR alone. Withholding of other therapies besides CPR and withdrawal of support are infrequent. Medical paternalism predominates in decision making.