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Background: The aim of this paper was to investigate the effectiveness of three different recruitment maneuvers (RMs) on respiratory and hemodynamic indexes, in patients with acute respiratory distress syndrome (ARDS), and determine the impact of patients' body mass index (BMI) on RMs efficacy., Methods: This was a prospective clinical trial conducted in a general intensive care unit. In 25 consecutive early ARDS patients arterial blood gases, respiratory system elastance (Est,rs) and hemodynamics were monitored before (T(0)), and at 3, 15, and 30 min (T(3), T(15), T(30), respectively) after each of three different RMs techniques with same airway pressures (45 cmH(2)O), randomly applied in each patient; RM-1: pressure control ventilation for 1 min, RM-2: two hyperinflations with continuous positive airway pressure for 20 sec and 1 min interval in between, RM-3: three consecutive sighs., Results: All RMs improved oxygenation and Est,rs shortly (T(3)) after their application, but only RM-2 had a prolonged beneficial effect on oxygenation (T(30)). Patients were further divided according to their BMI: in the low BMI group (<27.3 Kg/m(2)) the effectiveness of RMs was similar to the whole study population, while in the high BMI group (≥ 27.3 Kg/m(2)) no sustained effect followed any RM., Conclusion: In our cohort, recruitment by two sustained inflations resulted in a more persistent improvement of oxygenation as compared with recruitment by pressure controlled ventilation or consecutive sighs with the same airway pressure. BMI seems to have an impact on RMs effectiveness, most probably by altering the effective transpulmonary pressure. More studies are required to elucidate this observation.

Background: Several reports have shown that homocysteine promotes thrombosis by disturbing the procoagulant-anticoagulant balance, whereas alterations in coagulation and fibrinolysis have been suggested as important pathogenetic and prognostic determinants of mortality in acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). The objective of the study was to evaluate the effect of plasma homocysteine levels on the outcomes of patients with ALI/ARDS., Methods: Sixty-nine consecutive ventilated patients with ALI/ARDS were studied. Blood samples were drawn within 3 days of clinical recognition of ARDS. Measurement of plasma homocysteine, vitamin B12, folate, creatinine, protein C and plasminogen-activator inhibitor-1 antigen levels, and genotyping of the methylenetetrahydrofolate reductase gene C677T and A1298C polymorphisms were carried out. The primary outcomes were 28- and 90-day mortality, whereas secondary outcomes included nonpulmonary organ failure-free days, liberation from mechanical ventilation up to day 28, and ventilator-free days during the 28 days after enrollment., Results: In the multivariable analysis, plasma homocysteine concentration adjusted for age, Acute Physiology and Chronic Health Evaluation II score, methylenetetrahydrofolate reductase C677T and A1298C polymorphisms, and levels of plasminogen-activator inhibitor-1 antigen, protein C, creatinine, vitamin B12, and folate was not found to affect significantly mortality at 28 and 90 days (P = 0.39 and P = 0.83, respectively), days without organ failure besides lungs (P = 0.38), the probability of being free from mechanical ventilation at day 28 (P = 0.63), and days without ventilation assistance (P = 0.73)., Conclusion: Our data suggest that increased plasma homocysteine levels, either alone or in synergy with other thrombophilic risk factors, do not seem to adversely affect the prognosis in patients with ALI/ARDS.

Introduction: Increased levels of plasminogen activator inhibitor-1 (PAI-1) have been associated with worse outcome in ALI/ARDS. A single guanosine insertion/deletion (4G/5G) polymorphism in the promoter region of the PAI-1 gene, may play an important role in the regulation of PAI-1 expression. The objective of the study was to evaluate the effect of this polymorphism on the outcome of critically ill patients with ALI/ARDS., Materials and Methods: 52 consecutive ventilated patients with ALI/ARDS were studied. Bronchoalveolar lavage was performed within 48 hours from diagnosis. Measurement of plasma and BALF PAI-1 activity and D-dimers levels, and 4G/5G genotyping of PAI-1 were carried out. The primary outcome was 28-day mortality, and secondary outcomes included organ dysfunction and ventilator-free days., Results: 17 patients were homozygotes for the 4G allele. Severity scores were not different between subgroups upon study enrollment. 28-day mortality was 70.6% and 42.9% for the 4G-4G and the non-4G-4G patients, respectively (p=0.06). PAI-1 activity levels and D-dimer in plasma and BALF were not significantly different between the 4G-4G and the non-4G-4G subgroups. In the multivariate analysis, genotype 4G/4G was the only variable independently associated with 28-day mortality (Odds Ratio=9.95, 95% CI: 1.79-55.28, p=0.009). Furthermore, genotype 4G/4G and plasma PAI-1 activity levels were independently negatively associated with ventilator free days (p=0.033 and p=0.008, respectively)., Conclusions: ALI/ARDS patients, homozygous for the 4G allele of the PAI-1 gene, experienced higher 28-day mortality. This genotype was associated with a reduction in the number of days of unassisted ventilation and was inversely associated with the number of days without organ failure.

Objective: To assess respiratory mechanics on the 1st and 5th days of mechanical ventilation in a cohort of brain-damaged patients on positive end-expiratory pressure (PEEP) of 8 cmH(2)O or zero PEEP (ZEEP)., Design and Setting: Physiological study with randomized control trial design in a multidisciplinary intensive care unit of a university hospital., Patients and Measurements: Twenty-one consecutive mechanically ventilated patients with severe brain damage and no acute lung injury were randomly assigned to be ventilated with ZEEP (n = 10) or with 8 cmH(2)O of PEEP (n = 11). Respiratory mechanics and arterial blood gases were assessed on days 1 and day 5 of mechanical ventilation., Results: In the ZEEP group on day 1 static elastance and minimal resistance were above normal limits (18.9 +/- 3.8 cmH(2)O/l and 5.6 +/- 2.2 cmH(2)O/l per second, respectively); on day 5 static elastance and iso-CO(2) minimal resistance values were higher than on day 1 (21.2 +/- 4.1 cmH(2)O/l; 7.0 +/- 1.9 cmH(2)O/l per second, respectively). In the PEEP group these parameters did not change significantly. One of the ten patients on ZEEP developed acute lung injury. On day 5 there was a significant decrease in PaO(2)/FIO(2) in both groups., Conclusions: On day 1 of mechanical ventilation patients with brain damage exhibit abnormal respiratory mechanics. After 5 days of mechanical ventilation on ZEEP static elastance and minimal resistance increased significantly, perhaps reflecting "low lung volume" injury. Both could be prevented by administration of moderate levels of PEEP.

Background: Pulmonary endothelium is an active organ possessing numerous physiological, immunological, and metabolic functions. These functions may be altered early in acute lung injury (ALI) and further contribute to the development of acute respiratory distress syndrome (ARDS). Pulmonary endothelium is strategically located to filter the entire blood before it enters the systemic circulation; consequently its integrity is essential for the maintenance of adequate homeostasis in both the pulmonary and systemic circulations. Noxious agents that affect pulmonary endothelium induce alterations in hemodynamics and hemofluidity, promote interactions with circulating blood cells, and lead to increased vascular permeability and pulmonary edema formation., Objective: We highlight pathogenic mechanisms of pulmonary endothelial injury and their clinical implications in ALI/ARDS patients.

Background: Pulmonary capillary endothelium-bound (PCEB) angiotensin-converting ectoenzyme (ACE) activity alteration is an early, sensitive, and quantifiable lung injury index in animal models. We hypothesized that (1) PCEB-ACE alterations can be found in patients with acute lung injury (ALI) and (2) PCEB-ACE activity correlates with the severity of lung injury and may be used as a quantifiable marker of the underlying pulmonary capillary endothelial dysfunction., Methods and Results: Applying indicator-dilution techniques, we measured single-pass transpulmonary hydrolysis of the synthetic ACE substrate (3)H-benzoyl-Phe-Ala-Pro (BPAP) in 33 mechanically ventilated, critically ill patients with a lung injury score (LIS) ranging from 0 (no lung injury) to 3.7 (severe lung injury) and calculated the kinetic parameter A(max)/K(m). Both parameters decreased early during the ALI continuum and were inversely related to APACHE II score and LIS. Hydrolysis decreased with increasing cardiac output (CO), whereas 2 different patterns were observed between CO and A(max)/K(m)., Conclusions: PCEB-ACE activity decreases early during ALI, correlates with the clinical severity of both the lung injury and the underlying disease, and may be used as a quantifiable marker of underlying pulmonary capillary endothelial dysfunction.

Objective: Changes in pulmonary blood flow rate can alter the size of the perfused pulmonary capillary surface area. We tested the hypothesis that full recruitment of the pulmonary vascular bed may decrease evidence of lung injury by recruiting less injured capillaries. We also tested the hypothesis that endothelial ectoenzyme activity is an earlier indicator of lung injury than are permeability measures., Design: Isolated canine lung lobes were perfused with autologous blood at constant blood flows of either 2.05+/-0.04 L/min (SEM) (high flow, full recruitment, n = 12) or 0.600 +/- 0.004 L/min (low flow, 33% full recruitment, n = 12) after lung injury to determine the effect of vascular recruitment on measures of injury., Setting: Research laboratory at a medical university., Subjects: Lung lobes were obtained from 36 mongrel dogs of either gender., Interventions: Lung injury was induced by adding phorbol myristate acetate (PMA) to the blood perfusing the isolated lung., Measurements and Main Results: Indicator dilution methods were used to measure single pass hydrolysis of 3[H]-benzoyl-Phe-Ala-Pro, a synthetic substrate for angiotensin converting enzyme, and calculate the modified first order kinetic parameter corresponding to the ratio of a normalized maximal enzymatic conversion rate (A(max)) to the Michaelis-Menten constant (K(m)), i.e., A(max)/K(m), before and after PMA. At a given flow rate, the decrease in A(max)/K(m)serves as an index of vascular injury. PMA decreased A(max)/K(m), percent metabolism, and fractional substrate utilization, and increased permeability, vascular resistance, and vascular pressures regardless of flow rate. The decrease in enzyme activity was detected earlier than the increase in permeability., Conclusion: The greater percentage decrease in percent metabolism and fractional substrate utilization and the earlier appearance of increased permeability during high flow indicates that increasing blood flow three-fold recruited injured vessels and/or increased vascular injury by increasing vascular perfusion pressures.