Effect of blood-sugar limitation on intensive care mortality: Intragroup evaluation.

OBJECTIVE: To evaluate the safety profile of blood sugar limits in intensive care unit (ICU) patients. METHODS: Adult patients with ICU stay >36 h, more than two blood sugar measurements and antibiotic therapy concordant with locally adapted guidelines were included. For analyses, one study cohort was defined in two ways: as a narrow group, euglycaemic patients' blood sugar levels 80-150 mg/dl; as a moderate group, euglycaemic patients' blood sugar levels 80-180 mg/dl. Dysglycaemia was defined as blood sugar levels <80 mg/dl for >5% of measurements, and >150 mg/dl or >180 mg/dl (narrow or moderate groups, respectively) for >10% of measurements. The primary endpoint was ICU mortality (euglycaemia versus dysglycaemia). RESULTS: The study comprised 668 patients. When defined as a narrow group, ICU mortality was 3% (four of 135) euglycaemic versus 10% (54/533) dysglycaemic patients (odds ratio [OR] 3.692, 95% confidence interval [CI] 1.313, 10.382). When defined as a moderate group, ICU mortality was 6% (21/351) euglycaemic versus 12% (37/317) dysglycaemic patients (OR 2.077, 95% CI 1.188, 3.630). Frequency of severe hypoglycaemia (blood sugar <40 mg/dl) was not different between the narrow and moderate euglycaemic ranges. CONCLUSIONS: Euglycaemia was associated with lower ICU mortality than dysglycaemia, and incidence of hypoglycaemia was low overall in this study. Based on current published evidence, therapeutic targets should be defined according to individual patient characteristics.

Randomized controlled clinical trial evaluating multiplex polymerase chain reaction for pathogen identification and therapy adaptation in critical care patients with pulmonary or abdominal sepsis.

OBJECTIVE: To determine whether a multiplex polymerase chain reaction (PCR)-based test could reduce the time required for initial pathogen identification in patients in an intensive care unit (ICU) setting. METHODS: This double-blind, parallel-group randomized controlled trial** enrolled adults with suspected pulmonary or abdominal sepsis caused by an unknown pathogen. Both the intervention and control groups underwent the standard blood culture (BC) testing, but additional pathogen identification, based on the results of a LightCycler® SeptiFast PCR test, were provided in the intervention group. RESULTS: The study enrolled 37 patients in the control group and 41 in the intervention group. Baseline clinical and demographic characteristics were similar in both groups. The PCR-based test identified a pathogen in 10 out of 41 (24.4%) patients in the intervention group, with a mean duration from sampling to providing the information to the ICU of 15.9 h. In the control group, BC results were available after a significantly longer period (38.1 h). CONCLUSION: The LightCycler® SeptiFast PCR test demonstrated a significant reduction in the time required for initial pathogen identification, compared with standard BC.

Standard operating procedures for antibiotic therapy and the occurrence of acute kidney injury: a prospective, clinical, non-interventional, observational study.

INTRODUCTION: Acute kidney injury (AKI) occurs in 7% of hospitalized and 66% of Intensive Care Unit (ICU) patients. It increases mortality, hospital length of stay, and costs. The aim of this study was to investigate, whether there is an association between adherence to guidelines (standard operating procedures (SOP)) for potentially nephrotoxic antibiotics and the occurrence of AKI. METHODS: This study was carried out as a prospective, clinical, non-interventional, observational study. Data collection was performed over a total of 170 days in three ICUs at Charité - Universitaetsmedizin Berlin. A total of 675 patients were included; 163 of these had therapy with vancomycin, gentamicin, or tobramycin; were >18 years; and treated in the ICU for >24 hours. Patients with an adherence to SOP >70% were classified into the high adherence group (HAG) and patients with an adherence of <70% into the low adherence group (LAG). AKI was defined according to RIFLE criteria. Adherence to SOPs was evaluated by retrospective expert audit. Development of AKI was compared between groups with exact Chi2-test and multivariate logistic regression analysis (two-sided P <0.05). RESULTS: LAG consisted of 75 patients (46%) versus 88 HAG patients (54%). AKI occurred significantly more often in LAG with 36% versus 21% in HAG (P = 0.035). Basic characteristics were comparable, except an increased rate of soft tissue infections in LAG. Multivariate analysis revealed an odds ratio of 2.5-fold for LAG to develop AKI compared with HAG (95% confidence interval 1.195 to 5.124, P = 0.039). CONCLUSION: Low adherence to SOPs for potentially nephrotoxic antibiotics was associated with a higher occurrence of AKI. TRIAL REGISTRATION: Current Controlled Trials ISRCTN54598675. Registered 17 August 2007.

Polymorphisms of the toll-like receptor 2 and 4 genes are associated with faster progression and a more severe course of sepsis in critically ill patients.

OBJECTIVE: To determine whether the Arg753Gln polymorphism of the toll-like receptor 2 (TLR2) gene and the Asp299Gly polymorphism of the TLR4 gene in critically ill patients affect their clinical outcomes. METHODS: Medical and surgical patients in three intensive care units (ICU) were enrolled in this prospective study. TLR2 and TLR4 gene polymorphisms were determined using restriction fragment length polymorphism analysis. RESULTS: A total of 145 patients were included in this study: 28 patients carried heterozygous mutations (10 in the TLR2 gene, 19 in the TLR4 gene, and one combined) and 117 patients were wild type. Severe sepsis was observed in 33% of wild types (n = 38), 60% of the TLR2 group (n = 6), and 63% of the TLR4 group (n = 12); the difference was significant between the TLR4 and wild type groups. Both TLR groups demonstrated a shorter time-to-onset of severe sepsis or septic shock. Only the TLR4 group demonstrated significant progression towards septic shock compared with the wild type group. Length of ICU stay was significantly prolonged in the TLR4 group compared with the wild type group, but not in the TLR2 group. CONCLUSIONS: Two common SNPs of the TLR2 and TLR4 genes--Arg753Gln and Asp299Gly--were associated with a shorter time-to-onset of severe sepsis or septic shock in patients admitted to the ICU.

Gender-related outcome difference is related to course of sepsis on mixed ICUs: a prospective, observational clinical study.

INTRODUCTION: Impact of gender on severe infections is in highly controversial discussion with natural survival advantage of females described in animal studies but contradictory to those described human data. This study aims to describe the impact of gender on outcome in mixed intensive care units (ICUs) with a special focus on sepsis. METHODS: We performed a prospective, observational, clinical trial at Charité University Hospital in Berlin, Germany. Over a period of 180 days, patients were screened, undergoing care in three mainly surgical ICUs. In total, 709 adults were included in the analysis, comprising the main population ([female] n = 309, [male] n = 400) including 327 as the sepsis subgroup ([female] n = 130, [male] n = 197). RESULTS: Basic characteristics differed between genders in terms of age, lifestyle factors, comorbidities, and SOFA-score (Sequential Organ Failure Assessment). Quality and quantity of antibiotic therapy in means of antibiotic-free days, daily antibiotic use, daily costs of antibiotics, time to antibiotics, and guideline adherence did not differ between genders. ICU mortality was comparable in the main population ([female] 10.7% versus [male] 9.0%; P = 0.523), but differed significantly in sepsis patients with [female] 23.1% versus [male] 13.7% (P = 0.037). This was confirmed in multivariate regression analysis with OR = 1.966 (95% CI, 1.045 to 3.701; P = 0.036) for females compared with males. CONCLUSIONS: No differences in patients' outcome were noted related to gender aspects in mainly surgical ICUs. However, for patients with sepsis, an increase of mortality is related to the female sex.

Impact of adherence to standard operating procedures for pneumonia on outcome of intensive care unit patients.

BACKGROUND: Pneumonia accounts for almost half of intensive care unit (ICU) infections and nearly 60% of deaths from nosocomial infections. It increases hospital stay by 7-9 days, crude mortality by 70% and attributable mortality by 30%. OBJECTIVE: Our purpose was to assess the impact of standard operating procedures adapted to the local resistance rates in the initial empirical treatment for pneumonia on duration of first pneumonia episode, duration of mechanical ventilation, and length of ICU stay. DESIGN: Prospective observational cohort study with retrospective expert audit. SETTING: Five anesthesiologically managed ICUs at University hospital (one cardio-surgical, one neurosurgical, two interdisciplinary, and one intermediate care). PATIENTS: Of 524 consecutive patients with > or = 36 hr ICU treatment 131 patients with pneumonia on ICU were identified. Their first pneumonia episode was evaluated daily for adherence to standard operating procedures. Pneumonia was diagnosed according to the American Thoracic Society guidelines. Patients with > 70% compliance were assigned to high adherence group (HAG), patients with < or = 70% to low adherence group (LAG). MEASUREMENTS AND RESULTS: HAG consisted of 45 (49 first episode) patients, LAG of 86 (82 first episode) patients, respectively. Mean duration of treatment of the first pneumonia episode was 10.11 +/- 7.95 days in the LAG and 6.22 +/- 3.27 days in the HAG (p = 0.001). Duration of mechanical ventilation was 317.59 +/- 336.18 hrs in the LAG and 178.07 +/- 191.33 hrs in the HAG (p = 0.017). Length of ICU stay was 20.24 +/- 16.59 days in the LAG and 12.04 +/- 10.42 days in the HAG (p = 0.001). LIMITATIONS: Barriers in compliance need further evaluation. CONCLUSION: Adherence to standard operating procedure is associated with a shorter duration of treatment of first pneumonia episode, a shorter duration of mechanical ventilation, and a shorter ICU stay.