Genetic predisposition to acute respiratory distress syndrome in patients with severe sepsis

The objective of this study was to analyze the association between candidate gene polymorphisms and susceptibility to acute respiratory distress syndrome (ARDS) in patients with severe sepsis. Patients older than 18 years admitted to the intensive care un

Update in the management of critically ill burned patients

The management of critically ill burn patients is challenging. These patients have to be managed in specialized centers, where the expertise of physicians and nursing personnel guarantees the best treatment. Mortality of burn patients has improved over the past decades due to a better understanding of burn shock pathophysiology, optimal surgical management, infection control and nutritional support. Indeed, a more aggressive resuscitation, early excision and grafting, the judicious use of topical antibiotics, and the provision of an adequate calorie and protein intake are key to attain best survival results. General advances in critical care have also to be implemented, including protective ventilation, glycemic control, selective decontamination of the digestive tract, and implementation of sedation protocols.

Inhibition of nitro-oxidative stress attenuates pulmonary and systemic injury induced by high-tidal volume mechanical ventilation

Mechanisms contributing to pulmonary and systemic injury induced by high tidal volume (VT) mechanical ventilation are not well known. We tested the hypothesis that increased peroxynitrite formation is involved in organ injury and dysfunction induced by mechanical ventilation. Male Sprague-Dawley rats were subject to low- (VT, 9 mL/kg; positive end-expiratory pressure, 5 cmH2O) or high- (VT, 25 mL/kg; positive end-expiratory pressure, 0 cmH2O) VT mechanical ventilation for 120 min, and received 1 of 3 treatments: 3-aminobenzamide (3-AB, 10 mg/kg, intravenous, a poly adenosine diphosphate ribose polymerase [PARP] inhibitor), or the metalloporphyrin manganese(III) tetrakis(1-methyl-4-pyridyl)porphyrin (MnTMPyP, 5 mg/kg intravenous, a peroxynitrite scavenger), or no treatment (control group), 30 min before starting the mechanical ventilation protocol (n = 8 per group, 6 treatment groups). We measured mean arterial pressure, peak inspiratory airway pressure, blood chemistry, and gas exchange. Oxidation (fluorescence for oxidized dihydroethidium), protein nitration (immunofluorescence and Western blot for 3-nitrotyrosine), PARP protein (Western blot) and gene expression of the nitric oxide (NO) synthase (NOS) isoforms (quantitative real-time reverse transcription polymerase chain reaction) were measured in lung and vascular tissue. Lung injury was quantified by light microscopy. High-VT mechanical ventilation was associated with hypotension, increased peak inspiratory airway pressure, worsened oxygenation; oxidation and protein nitration in lung and aortic tissue; increased PARP protein in lung; up-regulation of NOS isoforms in lung tissue; signs of diffuse alveolar damage at histological examination. Treatment with 3AB or MnTMPyP attenuated the high-VT mechanical ventilation-induced changes in pulmonary and cardiovascular function; down-regulated the expression of NOS1, NOS2, and NOS3; decreased oxidation and nitration in lung and aortic tissue; and attenuated histological changes. Increased peroxynitrite formation is involved in mechanical ventilation-induced pulmonary and vascular dysfunction.

Characteristics of microRNAs and their potential relevance for the diagnosis and therapy of the acute respiratory distress syndrome: from bench to bedside

Acute respiratory distress syndrome (ARDS) is a complex disease associated with high morbidity and mortality. Biomarkers and specific pharmacologic treatment of the syndrome are lacking. MicroRNAs (miRNAs) are small (∼19–22 nucleotides) noncoding RNA molecules whose function is the regulation of gene expression. Their uncommon biochemical characteristics (eg, their resistance to degradation because of extreme temperature and pH fluctuations, freeze-thaw cycles, long storage times in frozen conditions, and RNAse digestion) and their presence in a wide range of different biological fluids and the relatively low number of individual miRNAs make these molecules good biomarkers in different clinical conditions. In addition, miRNAs are suitable therapeutic targets as their expression can be modulated by different available strategies. The aim of the present review is to offer clinicians a global perspective of miRNA, covering their structure and nomenclature, biogenesis, effects on gene expression, regulation of expression, and features as disease biomarkers and therapeutic targets, with special attention to ARDS. Because of the early stage of research on miRNAs applied to ARDS, attention has been focused on how knowledge sourced from basic and translational research could inspire future clinical studies.

Acute respiratory distress syndrome: does histology matter?

Kao et al. have reported in Critical Care the histological findings of 101 patients with acute respiratory distress syndrome (ARDS) undergoing open lung biopsy. Diffuse alveolar damage (DAD), the histological hallmark of ARDS, was present in only 56.4 % of cases. The presence of DAD was associated with higher mortality. Evidence from this and other studies indicates that the clinical criteria for the diagnosis of ARDS identify DAD in only about half of the cases. On the contrary, there is evidence that the clinical course and outcome of ARDS differs in patients with DAD and in patients without DAD. The discovery of biomarkers for the physiological (increased alveolocapillary permeability) or histological (DAD) hallmarks of ARDS is thus of paramount importance.

Using multivariate sequential patterns to improve survival prediction in intensive care burn unit

Resuscitation and stabilization are key issues in Intensive Care Burn Units and early survival predictions help to decide the best clinical action during these phases. Current survival scores of burns focus on clinical variables such as age or the body surface area. However, the evolution of other parameters (e.g. diuresis or fluid balance) during the first days is also valuable knowledge. In this work we suggest a methodology and we propose a Temporal Data Mining algorithm to estimate the survival condition from the patient’s evolution. Experiments conducted on 480 patients show the improvement of survival prediction.

The effects of prone position ventilation on experimental mild acute lung injury induced by intraperitoneal lipopolysaccharide injection in rats

The benefits of prone position ventilation are well demonstrated in the severe forms of acute respiratory distress syndrome, but not in the milder forms. We investigated the effects of prone position on arterial blood gases, lung inflammation, and histology in an experimental mild acute lung injury (ALI) model. ALI was induced in Wistar rats by intraperitoneal Escherichia coli lipopolysaccharide (LPS, 5 mg/kg). After 24 h, the animals with PaO2/FIO2 between 200 and 300 mmHg were randomized into 2 groups: prone position (n = 6) and supine position (n = 6). Both groups were compared with a control group (n = 5) that was ventilated in the supine position. All of the groups were ventilated for 1 h with volume-controlled ventilation mode (tidal volume = 6 ml/kg, respiratory rate = 80 breaths/min, positive end-expiratory pressure = 5 cmH2O, inspired oxygen fraction = 1). Significantly higher lung injury scores were observed in the LPS-supine group compared to the LPS-prone and control groups (0.32 ± 0.03; 0.17 ± 0.03 and 0.13 ± 0.04, respectively) (p < 0.001), mainly due to a higher neutrophil infiltration level in the interstitial space and more proteinaceous debris that filled the airspaces. Similar differences were observed when the gravity-dependent lung regions and non-dependent lung regions were analyzed separately (p < 0.05). The BAL neutrophil content was also higher in the LPS-supine group compared to the LPS-prone and control groups (p < 0.05). There were no significant differences in the wet/dry ratio and gas exchange levels. In this experimental extrapulmonary mild ALI model, prone position ventilation for 1 h, when compared with supine position ventilation, was associated with lower lung inflammation and injury.