22 Oct 08
Posted in ALI/ARDS at 10:50 by Laci
By T Mauri, A Coppadoro, G Bellani, M Bombino, N Patroniti, G Peri, A Mantovani, A Pesenti
Crit Care Med 2008;36:2302-2308
Pentraxin 3 is a fluid phase receptor involved in innate immunity. It belongs to the Pentraxins family, as C-reactive protein does. Pentraxin 3 is produced by a variety of tissue cells, whereas only the liver produces C-reactive protein. Pentraxin 3 plays a unique role in the regulation of inflammation. Acute lung injury and acute respiratory distress syndrome are characterized by an important inflammatory reaction. We investigated the role of pentraxin 3 as a marker of severity and outcome predictor of acute lung injury and acute respiratory distress syndrome.
Design
We measured circulating pentraxin 3 and C-reactive protein levels within 24 hrs from intubation (day 1), after 24 hrs from the first sample, then every 3 days for the first month and then once a week, until discharge from the intensive care unit. Pentraxin 3 was also measured in bronchoalveolar lavages, performed when clinically indicated.
Setting
One university medical center general intensive care unit.
Patients
The study included 21 patients affected by acute lung injury and acute respiratory distress syndrome (1994 Consensus Conference criteria).
Interventions
None.
Measurements and main results
Pentraxin 3 plasma levels were high with a peak on the first day (median 71.05 ng/mL, interquartile range 52.37-117.38 ng/mL, normal values <2 ng/mL), declining thereafter. C-reactive protein peaked later and remained at relatively high values. Out of several day 1 parameters, pentraxin 3 was the only significant difference between survivors and nonsurvivors. Pentraxin 3 levels were positively correlated with lung injury score values (p < 0.001) and number of organ failures (p < 0.001). Pentraxin 3 was present in bronchoalveolar lavages fluids (5.03 ng/mL, interquartile range 1.52-8.48 ng/mL) and bronchoalveolar lavages positive to bacterial culture were associated with significantly higher pentraxin 3 values (p < 0.05).
Conclusions
The results presented here show that pentraxin 3 is elevated in acute lung injury and acute respiratory distress syndrome and that its levels correlate with parameters of lung injury and systemic involvement. The clinical and pathophysiological significance of pentraxin 3 in acute lung injury and acute respiratory distress syndrome deserves further scrutiny.
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07 Sep 08
Posted in ALI/ARDS, BNP at 19:28 by Laci
By EK Bajwa, JL Januzzi, MN Gong, BT Thompson, DC Christiani
Crit Care Med 2008;36:2322-2327
Patients with acute respiratory distress syndrome suffer from profound cardiac and pulmonary derangement, including right ventricular strain and noncardiogenic pulmonary edema, which may potentially alter concentrations of cardiac natriuretic peptides. We sought to determine whether N-terminal probrain natriuretic peptide (NT-proBNP) levels are elevated in acute respiratory distress syndrome and whether they can serve as a marker of prognosis in this setting.
Design
Prospective study.
Setting
Tertiary-care academic medical center.
Patients
One hundred seventy-seven acute respiratory distress syndrome subjects enrolled in a prospective intensive care unit cohort.
Interventions
None
Measurements and main results
NT-proBNP was measured from blood taken within 48 hrs of acute respiratory distress syndrome onset. Patients were followed for the primary outcome of 60-day mortality and secondary outcomes of organ dysfunction and ventilator-free days. Seventy patients died (40%). Median NT-proBNP level was 3181 ng/L (interquartile range 723-9246 ng/L). NT-proBNP levels were significantly higher among nonsurvivors (p < .0001). Receiver operating curve analysis revealed an optimal NT-proBNP cut-point of 6813 ng/L for predicting death. Patients with levels above the cut-point had significantly higher odds of mortality on multivariable analysis (odds ratio 2.36, 95% confidence interval 1.11-4.99, p = .02) than those with levels below the cut-point. Kaplan-Meier survival analysis showed that this difference emerged early and was sustained (p < .0001). Patients with elevated NT-proBNP also had higher organ dysfunction scores (p < .0001) and fewer ventilator free days (p = .03) than those with lower NT-proBNP levels.
Conclusions
NT-proBNP levels are elevated among acute respiratory distress syndrome patients and parallel the severity of the syndrome and likelihood for morbidity and mortality. This demonstrates the potential utility of this biomarker for prognosis in this disease.
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15 Jun 08
Posted in ALI/ARDS, Mechanical ventilation at 10:07 by Laci
By M O Meade, D J Cook, G H Guyatt, A S Slutsky, Y M Arabi, J Cooper, A R Davies, L E Hand et al for the Lung Open Ventilation Study Investigators
JAMA 2008;299:637-645
Low-tidal-volume ventilation reduces mortality in critically ill patients with acute lung injury and acute respiratory distress syndrome. Instituting additional strategies to open collapsed lung tissue may further reduce mortality.
Objective
To compare an established low-tidal-volume ventilation strategy with an experimental strategy based on the original “open-lung approach,” combining low tidal volume, lung recruitment maneuvers, and high positive-end–expiratory pressure.
Design and setting
Randomized controlled trial with concealed allocation and blinded data analysis conducted between August 2000 and March 2006 in 30 intensive care units in Canada, Australia, and Saudi Arabia.
Patients
Nine hundred eighty-three consecutive patients with acute lung injury and a ratio of arterial oxygen tension to inspired oxygen fraction not exceeding 250.
Interventions
The control strategy included target tidal volumes of 6 mL/kg of predicted body weight, plateau airway pressures not exceeding 30 cm H2O, and conventional levels of positive end-expiratory pressure (n = 508). The experimental strategy included target tidal volumes of 6 mL/kg of predicted body weight, plateau pressures not exceeding 40 cm H2O, recruitment maneuvers, and higher positive end-expiratory pressures (n = 475).
Main outcome measure
All-cause hospital mortality.
Results
Eighty-five percent of the 983 study patients met criteria for acute respiratory distress syndrome at enrollment. Tidal volumes remained similar in the 2 groups, and mean positive end-expiratory pressures were 14.6 (SD, 3.4) cm H2O in the experimental group vs 9.8 (SD, 2.7) cm H2O among controls during the first 72 hours (P < .001). All-cause hospital mortality rates were 36.4% and 40.4%, respectively (relative risk [RR], 0.90; 95% confidence interval [CI], 0.77-1.05; P = .19). Barotrauma rates were 11.2% and 9.1% (RR, 1.21; 95% CI, 0.83-1.75; P = .33). The experimental group had lower rates of refractory hypoxemia (4.6% vs 10.2%; RR, 0.54; 95% CI, 0.34-0.86; P = .01), death with refractory hypoxemia (4.2% vs 8.9%; RR, 0.56; 95% CI, 0.34-0.93; P = .03), and previously defined eligible use of rescue therapies (5.1% vs 9.3%; RR, 0.61; 95% CI, 0.38-0.99; P = .045).
Conclusions
For patients with acute lung injury and acute respiratory distress syndrome, a multifaceted protocolized ventilation strategy designed to recruit and open the lung resulted in no significant difference in all-cause hospital mortality or barotrauma compared with an established low-tidal-volume protocolized ventilation strategy. This “open-lung” strategy did appear to improve secondary end points related to hypoxemia and use of rescue therapies.
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Posted in ALI/ARDS, Mechanical ventilation at 10:04 by Laci
By A Mercat, J-C Richard, B Vielle, S Jaber, D Osman, J-L Diehl, J-Y Lefrant et al for the Expiratory Pressure (Express) Study Group
JAMA. 2008;299:646-655
The need for lung protection is universally accepted, but the optimal level of positive end-expiratory pressure (PEEP) in patients with acute lung injury (ALI) or acute respiratory distress syndrome remains debated.
Objective
To compare the effect on outcome of a strategy for setting PEEP aimed at increasing alveolar recruitment while limiting hyperinflation to one aimed at minimizing alveolar distension in patients with ALI.
Design, setting and patients
A multicenter randomized controlled trial of 767 adults (mean [SD] age, 59.9 [15.4] years) with ALI conducted in 37 intensive care units in France from September 2002 to December 2005.
Intervention
Tidal volume was set at 6 mL/kg of predicted body weight in both strategies. Patients were randomly assigned to a moderate PEEP strategy (5-9 cm H(2)O) (minimal distension strategy; n = 382) or to a level of PEEP set to reach a plateau pressure of 28 to 30 cm H(2)O (increased recruitment strategy; n = 385).
Main outcome measures
The primary end point was mortality at 28 days. Secondary end points were hospital mortality at 60 days, ventilator-free days, and organ failure-free days at 28 days. RESULTS: The 28-day mortality rate in the minimal distension group was 31.2% (n = 119) vs 27.8% (n = 107) in the increased recruitment group (relative risk, 1.12 [95% confidence interval, 0.90-1.40]; P = .31). The hospital mortality rate in the minimal distension group was 39.0% (n = 149) vs 35.4% (n = 136) in the increased recruitment group (relative risk, 1.10 [95% confidence interval, 0.92-1.32]; P = .30). The increased recruitment group compared with the minimal distension group had a higher median number of ventilator-free days (7 [interquartile range {IQR}, 0-19] vs 3 [IQR, 0-17]; P = .04) and organ failure-free days (6 [IQR, 0-18] vs 2 [IQR, 0-16]; P = .04). This strategy also was associated with higher compliance values, better oxygenation, less use of adjunctive therapies, and larger fluid requirements.
Conclusions
A strategy for setting PEEP aimed at increasing alveolar recruitment while limiting hyperinflation did not significantly reduce mortality. However, it did improve lung function and reduced the duration of mechanical ventilation and the duration of organ failure.
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