Cell-cycle arrest biomarkers in urine to predict acute kidney injury in septic and non-septic critically ill patients.

PURPOSE: To analyse the usefulness of the composite index of the tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) as urinary biomarkers for the early prediction of AKI in septic and non-septic patients. METHODS: This is a prospective, observational study including patients admitted to ICU from acute care departments and hospital length of stay <48 h. The main exclusion criteria were pre-existing eGFR <30 mL/min/1.73 m2 and hospitalisation 2 months prior to current admission. The [TIMP-2]·[IGFBP7] index was analysed twice, within the first 12 h of ICU admission. RESULTS: The sample included 98 patients. AKI incidence during ICU stay was 50%. Sepsis was diagnosed in 40.8%. Baseline renal variables were comparable between subgroups except for a higher baseline eGFR in non-septic patients. Patients were stratified based on the presence of AKI and their highest level of [TIMP-2]·[IGFBP7] within the first 12 h of stay. [TIMP-2]·[IGFBP7] index values were dependent on the incidence of AKI but not of sepsis. [TIMP-2]·[IGFBP7] values were significantly related to AKI severity according to AKIN criteria (p < 0.0001). The AUROC curve to predict AKI of the worst [TIMP-2]·[IGFBP7] index value was 0.798 (sensitivity 73.5%, specificity 71.4%, p < 0.0001). Index values below 0.8 ruled out any need for renal replacement (NPV 100%), whereas an index >0.8 predicted a rate of AKI of 71% and AKIN ≥ 2 of 62.9%. CONCLUSIONS: In our study, urinary [TIMP-2]·[IGFBP7] was an early predictor of AKI in ICU patients regardless of sepsis. Besides, index values <0.8(ng/mL)2/1000 ruled out the need for renal replacement.

Non-invasive pressure support ventilation versus conventional oxygen therapy in acute cardiogenic pulmonary oedema: a randomised trial.

BACKGROUND: Non-invasive pressure support ventilation (NIPSV) is an effective treatment for acute respiratory failure in patients with chronic obstructive pulmonary disease. We assessed the efficacy of this therapy in acute cardiogenic pulmonary oedema in a randomised comparison with conventional oxygen therapy. METHODS: 40 patients were randomly assigned conventional oxygen therapy or NIPSV supplied by a standard ventilator through a face mask, with adjustment of tidal volume and pressure support in addition to a positive end-expiratory pressure of 5 cm water. Physiological measurements were obtained in the first 2 h and at 3 h, 4 h, and 10 h. The main endpoints were intubation rate and resolution time. Analyses were by intention to treat. FINDINGS: Three patients were withdrawn on the basis of clinical and chest radiography results. Endotracheal intubation was required in one (5%) of 19 patients assigned NIPSV and in six (33%) of 18 assigned conventional oxygen therapy (p=0.037). Resolution time (defined as a clinical improvement with oxygen saturation of 96% or more and respiratory rate less than 30 breaths/min) was significantly shorter in the NIPSV group (median 30 [IQR 15-53] vs 105 [50-230] min, p=0.002). NIPSV led to a rapid improvement in oxygenation in the first 2 h. There were no differences in hospital length of stay or mortality. INTERPRETATION: In this study of acute cardiogenic pulmonary oedema, NIPSV was superior to conventional oxygen therapy. Further studies should compare NIPSV with continuous positive airway pressure.

Serial surveillance cultures of skin and catheter hub specimens from critically ill patients with central venous catheters: molecular epidemiology of infection and implications for clinical management and research.

A prospective study of 45 central venous catheters was conducted to assess, by strain delineation, the turnover of skin and catheter hub (superficial) colonization and the relative contributions of catheter hub and skin colonization to catheter tip colonization. Serial quantitative cultures of skin and catheter hub were performed. Catheter tip, blood, and specimens for culture from targeted superficial sites (TSSs) were also collected at the time of catheter removal. Strains from 17 tip-positive catheters were delineated by pulsed-field gel electrophoresis. Only 12 (28.6%) of 42 skin strains and 14 (31.1%) of 45 catheter hub strains were found to be present at the time of catheter removal. In addition, only 9 (29.0%) of the 31 tip-colonizing strains were present on TSSs. Moreover, 15 (48.4%) of the 31 tip-colonizing strains had a superficial origin, and the other 16 (51.6%) were of unknown origin. In catheters suspected of infection, cultures of TSSs had a negative predictive value for catheter-related bacteremia of 94.4% but a positive predictive value of 44.4%. When the causative agent was identified (to the strain level) these values dropped to 80.9 and 18.7%, respectively. The study shows that skin and catheter hub colonization is a common, dynamic phenomenon. Strains recovered from TSSs showed a low level of correlation with strains from previous cultures of specimens from superficial sites and catheter tip isolates. Consequently, TSSs cannot be recommended for use in determining the therapy. However, catheter-related bacteremia is uncommon when cultures of TSSs are negative.

Short-term effects of prone position in critically ill patients with acute respiratory distress syndrome.

OBJECTIVE: Changing the position from supine to prone is an emerging strategy to improve gas exchange in patients with the acute respiratory distress syndrome (ARDS). The aim of this study was to evaluate the acute effects on gas exchange, hemodynamics, and respiratory system mechanics of turning critically ill patients with ARDS from supine to prone. DESIGN: Open, prospective study. SETTING: General intensive care units. PATIENTS: 23 patients [mean age 56 +/- 17 (SD) years] who met ARDS criteria and had a Lung Injury Score > 2.5 (mean 3.25 +/- 0.3). INTERVENTIONS: The decision to turn a patient was made using a protocol based on impaired oxygenation despite the use of positive end-expiratory pressure and a fractional inspired oxygen (FIO2) of 1. MEASUREMENTS AND RESULTS: We measured gas exchange and hemodynamic variables in all patients and in 16 patients calculated respiratory system compliance when they were supine and 60 to 90 min after turning them to a prone position. This latter position was remarkably well tolerated and no clinically relevant complications or events were detected either during turning or while prone. The partial pressure of oxygen in arterial blood (PaO2)/FIO2 ratio improved from 78 +/- 37 mm Hg supine to 115 +/- 31 mm Hg prone (p < 0.001), and intrapulmonary shunt decreased from 43 +/- 11 to 34 +/- 8% (p < 0.001). Cardiac output and other hemodynamic parameters were not affected. Respiratory system compliance slightly improved from 24.7 +/- 10.2 ml/cmH20 supine to 27.8 +/- 13.2 ml/cmH20 prone (p < 0.05). An improvement in PaO2/FIO2 of more than 15% from changing from supine to prone was found in 16 patients (responders). Responders had more hypoxemia (PaO2/FIO2 70 +/- 23 vs 99 +/- 53 mm Hg in non-responders, p < 0.01), more hypercapnia (partial pressure of carbon dioxide in arterial blood (70 +/- 27 vs 64 +/- 9 mm Hg, p < 0.01) and a shorter elapsed time to the onset of ARDS and turning to the prone position (11.8 +/- 16 vs 32.8 +/- 42 days, p < 0.01). CONCLUSIONS: Turning critically ill, severely hypoxemic patients from the supine to the prone position is a safe and useful therapeutic intervention. Our data suggest that prone positioning should be carried out early in the course of ARDS.

Prognostic indexes and mortality in critically ill patients with acute renal failure treated with different dialytic techniques.

The objective of this study was to compare the evolution of patients with acute renal failure (ARF) treated conservatively or with different dialytic techniques in an intensive care unit (ICU). From June 1992 to November 1994, 1087 consecutive patients were admitted in our ICU. Two hundred and twenty of these presented with ARF, and were divided into three groups; group I (control group): 156 patients with ARF who did not receive substitutive techniques; group II: 21 patients under intermittent hemodialysis (IHD) or peritoneal dialysis (PD); group III: 43 patients under continuous hemodiafiltration (CHDF). The studied variables were age, etiology of renal failure, requirement of dialysis, type of dialysis, length of ICU and hospital stay, and renal function outcome. APACHE II and SAPS scores were recorded on admission and analyzed for hospital mortality. Chi-square test and the analysis of variance were used for the statistical analysis. Results are presented as mean +/- SD. A p value below 0.05 was considered statistically significant. Although etiology of ARF was multifactorial, we found a high frequency of ARF due to sepsis (56.8%), hypoperfusion (58.7%), and acute tubular necrosis (62.5%). Sepsis and heart failure were clinical conditions associated to a greater mortality. We did not find any statistical difference between the two dialyzed groups for all the studied variables, nor between the three groups regarding APACHE II and hospital stay. Significant differences were found between dialyzed and non-dialyzed patients respect to age, group I: 64.1 +/- 13.6, group II: 56.4 +/- 19.7, and group III: 56.0 +/- 14.1 (p < 0.001), creatinine peak serum levels, group I: 260 +/- 130, group II: 494 +/- 209, and group III: 441 +/- 170 mumol/L (p < 0.0001), and mortality, group I: 46.9%, group II: 66.7%, and group III: 76.2% (p < 0.002). SAPS score showed differences between the control group and the CHDF group 13.9 +/- 4.8 and 16.4 +/- 5.4 (p < 0.007), respectively. The use of dialytic techniques in critically ill ARF patients is associated with greater mortality. Prognostic indexes on admission did not correctly classify our patients with ARF. Continuous hemodiafiltration does not involve greater mortality or length of stay as compared to conventional dialysis.

[Gas exchange and hemodynamic effects of nitric oxide inhalation in patients with acute respiratory distress syndrome]. / Efectos gasométricos y hemodinámicos de la inhalación de óxido nítrico en pacientes con síndrome de distrés respiratorio agudo.

BACKGROUND: To analyze the effects on gas exchange and hemodynamics of nitric oxide inhalation in patients with acute respiratory distress syndrome. PATIENTS AND METHODS: Prospective study including 16 acute respiratory distress syndrome patients. We analyzed the acute and short-term (5 days) effects of inhaling 5 parts per million (ppm) nitric oxide on gas exchange and hemodynamics. RESULTS: After nitric oxide inhalation, PaO2/FiO2 ratio changed from 81 +/- 25 to 126 +/- 57 mmHg (p = 0.0001), mean pulmonary artery pressure decreased from 30.1 +/- 8.2 to 27.3 +/- 6.6 mmHg (p = 0.002), intrapulmonary shunt decreased from 44.6 +/- 11% to 34.1 +/- 7.9% (p = 0.002) and cardiac index did not change. Thirteen out of 16 patients (81.2%) presented at least a 20% improvement in PaO2/FiO2 ratio. In the 10 patients treated over 5 consecutive days, we observed that those who improved (increase in PaO2/FiO2 ratio higher than 20% after inhaling 5 ppm nitric oxide) showed a lower cardiac index, a higher mean pulmonary artery pressure and a higher pulmonary vascular resistance index than those who did not: Cl 3.9 +/- 0.81 vs 4.9 +/- 0.81 l/min/m2 (p < 0.001), mean pulmonary artery pressure 32.4 +/- 7 vs 25.3 +/- 4.2 mmHg (p = 0.001), and pulmonary vascular resistance index 421 +/- 199 vs 241 +/- 106 dyn.s.cm5/m2 (p = 0.003). Mean levels of methemoglobin were 1.1 +/- 0.24% (range: 0.4-1.6%), and NO2 concentration was always lower than 100 parts per billion. CONCLUSIONS: Low doses of inhaled nitric oxide induce a selective pulmonary vasodilatation and significant improvement of oxygenation in the majority of acute respiratory distress syndrome patients, although those with a hyperkinetic hemodynamic status are less likely to improve the oxygenation. These effects are maintained for at least 5 days. We did not observe rebound effects.

[Clinical relevance of gram-negative bacteria having inducible chromosomic beta-lactamase at an intensive care unit]. / Relevancia clínica de las bacterias gramnegativas que poseen betalactamasa cromosómica inducible en una unidad de cuidados intensivos.

BACKGROUND: The aim of the study was to determine the frequency of third-generation cephalosporins and aztreonam resistance in gram-negative bacteria with inducible chromosomal beta-lactamase (beta Lac-ind) after beta-lactam therapy in the medical-surgical intensive care unit (ICU) at a university-affiliated hospital. PATIENTS AND METHODS: We studied 34 infections in 29 patients admitted to the ICU. All were infected by strains with beta Lac-ind and all were treated with beta-lactam antibiotics. Susceptibility was determined by disc-diffusion. The beta-lactamase activity of those strains showing constitutive beta-lactamase overproduction were characterized by isoelectrofocusing. When this derepression occurred during the therapy, the strains were compared by genomic macrorestriction (PGFE). RESULTS: In 29 out of 34 infections the initial strains was susceptible. In 11 cases, the culture were not negativized in spite of their susceptible pattern. In 4 cases there was derepression during therapy. In 5 cases the initial strains were derepressed. The microorganisms isolated more frequently were Pseudomonas aeruginosa (22 cases) and Enterobacter cloacae (5 cases). The beta-lactamase activity detected correspond well with a betaLac-ind. In those cases with derepression during therapy, the initial susceptible strain and the resistant strain were identical by PGFE.