22 Sep 07
Posted in ALI/ARDS, Steroid at 18:00 by Laci
By The National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network
N Engl J Med 2006;354:1671–1684 http://content.nejm.org/cgi/content/abstract/354/16/1671
Persistent acute respiratory distress syndrome (ARDS) is characterized by excessive fibroproliferation, ongoing inflammation, prolonged mechanical ventilation, and a substantial risk of death. Because previous reports suggested that corticosteroids may improve survival, we performed a multicenter, randomized controlled trial of corticosteroids in patients with persistent ARDS.
Methods
We randomly assigned 180 patients with ARDS of at least seven days’ duration to receive either methylprednisolone or placebo in a double-blind fashion. The primary end point was mortality at 60 days. Secondary end points included the number of ventilator-free days and organ-failure–free days, biochemical markers of inflammation and fibroproliferation, and infectious complications.
Results
At 60 days, the hospital mortality rate was 28.6 percent in the placebo group (95 percent confidence interval, 20.3 to 38.6 percent) and 29.2 percent in the methylprednisolone group (95 percent confidence interval, 20.8 to 39.4 percent; P=1.0); at 180 days, the rates were 31.9 percent (95 percent confidence interval, 23.2 to 42.0 percent) and 31.5 percent (95 percent confidence interval, 22.8 to 41.7 percent; P=1.0), respectively. Methylprednisolone was associated with significantly increased 60- and 180-day mortality rates among patients enrolled at least 14 days after the onset of ARDS. Methylprednisolone increased the number of ventilator-free and shock-free days during the first 28 days in association with an improvement in oxygenation, respiratory-system compliance, and blood pressure with fewer days of vasopressor therapy. As compared with placebo, methylprednisolone did not increase the rate of infectious complications but was associated with a higher rate of neuromuscular weakness.
Conclusions
These results do not support the routine use of methylprednisolone for persistent ARDS despite the improvement in cardiopulmonary physiology. In addition, starting methylprednisolone therapy more than two weeks after the onset of ARDS may increase the risk of death.
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02 Apr 07
Posted in ALI/ARDS, Mechanical ventilation at 20:18 by Laci
By I Toth, T Leiner, A Mikor, T Szakmany, L Bogar, Zs Molnar
Critical Care Medicine 2007;35:787-793
Objectives
To investigate respiratory and hemodynamic changes during lung recruitment and descending optimal positive end-expiratory pressure (PEEP) titration.
Design
Prospective auto-control clinical trial.
Setting
Adult general intensive care unit in a university hospital.
Patients
Eighteen patients with acute respiratory distress syndrome.
Interventions
Following baseline measurements (T0), PEEP was set at 26 cm H2O and lung recruitment was performed (40/40-maneuver). Then tidal volume was set at 4 mL/kg (T26R) and PEEP was lowered by 2 cmH2O in every 4 mins. Optimal PEEP was defined at 2 cmH2O above the PEEP where PaO2 dropped by >10%. After setting the optimal PEEP, the 40/40-maneuver was repeated and tidal volume set at 6 mL/kg (Tend).
Measurements and Main Results
Arterial blood gas analysis was done every 4 mins and hemodynamic measurements every 8 mins until Tend, then in 30 (T30) and 60 (T60) mins. The PaO2 increased from T0 to Tend (203 +/- 108 vs. 322 +/- 101 mm Hg, p < .001), but the extravascular lung water (EVLW) did not change significantly. Cardiac index (CI) and the intrathoracic blood volume (ITBV) decreased from T0 to T26R (CI, 3.90 +/- 1.04 vs. 3.62 +/- 0.91 L/min/m2, p < .05; ITBVI, 832 +/- 205 vs. 795 +/- 188 mL/m2, p < .05). There was a positive correlation between CI and ITBVI (r = .699, p < .01), a negative correlation between CI and central venous pressure (r = -.294, p < .01), and no correlation between CI and mean arterial pressure (MAP).
Conclusions
Following lung recruitment and descending optimal PEEP titration, the PaO2 improves significantly, without any change in the EVLW up to 1 hr. This suggests a decrease in atelectasis as a result of recruitment rather than a reduction of EVLW. There is a significant change in CI during the maneuver, but neither central venous pressure, heart rate, nor MAP can reflect these changes.
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27 Mar 07
Posted in ALI/ARDS at 18:53 by Laci
By N K J Adhikari, K E A Burns, J O Friedrich, J T Granton, D J Cook, M O Meade
BMJ, doi:10.1136/bmj.39139.716794.55
Objective
To review the literature on the use of inhaled nitric oxide to treat acute lung injury/acute respiratory distress syndrome (ALI/ARDS) and to summarise the effects of nitric oxide, compared with placebo or usual care without nitric oxide, in adults and children with ALI or ARDS.
Design
Systematic review and meta-analysis.
Data sources
Medline, CINAHL, Embase, and CENTRAL (to October 2006), proceedings from four conferences, and additional information from authors of 10 trials.
Review methods
Two reviewers independently selected parallel group randomised controlled trials comparing nitric oxide with control and extracted data related to study methods, clinical and physiological outcomes, and adverse events.
Main outcome measures
Mortality, duration of ventilation, oxygenation, pulmonary arterial pressure, adverse events.
Results
12 trials randomly assigning 1237 patients met inclusion criteria. Overall methodological quality was good. Using random effects models, we found no significant effect of nitric oxide on hospital mortality (risk ratio 1.10, 95% confidence interval 0.94 to 1.30), duration of ventilation, or ventilator-free days. On day one of treatment, nitric oxide increased the ratio of partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2 ratio) (13%, 4% to 23%) and decreased the oxygenation index (14%, 2% to 25%). Some evidence suggested that improvements in oxygenation persisted until day four. There was no effect on mean pulmonary arterial pressure. Patients receiving nitric oxide had an increased risk of developing renal dysfunction (1.50, 1.11 to 2.02).
Conclusions
Nitric oxide is associated with limited improvement in oxygenation in patients with ALI or ARDS but confers no mortality benefit and may cause harm. We do not recommend its routine use in these severely ill patients
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18 Mar 07
Posted in ALI/ARDS, Mechanical ventilation at 9:42 by Laci
By M Jain and J I Sznajder
Critical Care 2007, 11:206 doi:10.1186/cc5159
See related commentary by Pelosi and Rocco.
Distal airways are less than 2 mm in diameter, comprising a relatively large cross-sectional area that allows for slower, laminar airflow. The airways include both membranous bronchioles and gas exchange ducts, and have been referred to in the past as the ‘quiet zone’, in part because these structures were felt to contribute little to lung mechanics and in part because they were difficult to study directly. More recent data suggest that distal airway dysfunction plays a significant role in acute respiratory distress syndrome. In addition, injurious mechanical ventilation strategies may contribute to distal airway dysfunction. The presence of elevated airway resistance, intrinsic positive end-expiratory pressure or a lower inflection point on a pressure–volume curve of the respiratory system may indicate the presence of impaired distal airway function. There are no proven specific treatments for distal airway dysfunction, and protective ventilation strategies to minimize distal airway injury may be the best therapeutic approach at this time.
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