American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Oct 1999
Crucial role of group IIA phospholipase A(2) in oleic acid-induced acute lung injury in rabbits.
Group IIA secretory phospholipase A(2) (sPLA(2)) has been implicated in a variety of inflammatory diseases including acute lung injury (ALI); however, the role of sPLA(2) in this disorder remains unclear. The aim of the present investigation was to examine the role of this enzyme in a model of ALI induced by oleic acid (OA) in rabbits by testing human group IIA phospholipase A(2) (PLA(2)) inhibitor, S-5920/LY315920Na. Experimental groups consisted of a saline control group (n = 8), an OA control group (n = 10) infused intravenously with OA (0.1 ml/kg/h for 2 h), and three groups given OA + S-5920/LY315920Na (three different doses, n = 8, respectively). ⋯ Pretreatment with S-5920/LY315920Na diminished the OA-induced PLA(2) activity in the BALF and dose-dependently attenuated the previously described lung injury induced by OA, accompanied by protection against lung surfactant degradation and production of thromboxane A(2) (TXA(2)) and leukotriene B(4) (LTB(4)). S-5920/LY315920Na also inhibited the OA-induced production of interleukin-8 (IL-8), both in plasma and BALF. Thus, sPLA(2) appears to play a key role in OA-induced lung injury, suggesting that the group IIA PLA(2) inhibitor may be a promising agent for patients with acute respiratory distress syndrome (ARDS).
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Am. J. Respir. Crit. Care Med. · Sep 1999
Correcting static intrinsic positive end-expiratory pressure for expiratory muscle contraction. Validation of a new method.
We have recently shown (Eur. Respir. J. 1997;10:522-529) that in spontaneously breathing and actively expiring patients, static intrinsic positive end-expiratory pressure (PEEPi,st) can be corrected for expiratory muscle contraction by subtracting the average expiratory rise in gastric pressure (Pga,exp rise), calculated from three breaths just prior to an airway occlusion, from the end-expiratory airway pressure (Paw) of the first occluded inspiratory effort (PEEPi,st avg). ⋯ Coefficient of variation of Pga,exp rise was 14.3 +/- 7.2% (range, 5.2 to 28.3%). There was a good correlation between the coefficient of variation of Pga,exp rise and the difference between PEEPi,st avg and PEEPi,st ref (r = 0.909; p < 0.001). We conclude that PEEPi,st can be accurately measured in spontaneously breathing patients by synchronous subtraction of Pga,exp rise from Paw during airway occlusion.
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Am. J. Respir. Crit. Care Med. · Sep 1999
Randomized Controlled Trial Multicenter Study Clinical TrialImpact of immunomodulating therapy on morbidity in patients with severe sepsis.
We assessed the impact, over a 28-d period, of therapy with the tumor necrosis factor (TNF) neutralizing receptor fusion protein (p55-IgG) on the incidence of end-organ failures in patients with severe sepsis or early septic shock in a subgroup of 165 patients recruited into a randomized, multicenter clinical trial to receive placebo (n = 78) or a single infusion of p55-IgG, 0.083 mg/kg (n = 87). At study entry, distribution of organ dysfunctions and other baseline characteristics were similar for the two study groups. Treatment with p55-IgG was associated with a trend toward reduced 28-d mortality (p = 0.07), a decreased incidence of new organ dysfunctions (relative risk [RR], 0.57; 95% confidence interval [95% CI] 0.29 to 1.10, p = 0.10), and a decreased overall incidence-density of organ failures (RR 0.65; 95% CI 0.60 to 0.71, p = 0.0001). ⋯ For those patients who survived, this difference was 4.1 d (95% CI 1.6 to 6.6). Duration of ventilatory support was 3.2 d shorter (95% CI 0.1 to 6.3) among 28-d survivors who received p55-IgG, compared with placebo. In conclusion, in the population of septic patients studied, treatment with p55-IgG was associated with a trend toward shorter need for mechanical ventilatory support, a decreased length of stay (LOS), and a decreased incidence and duration of organ failure.
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Am. J. Respir. Crit. Care Med. · Sep 1999
Multicenter Study Comparative StudyAcute asthma among pregnant women presenting to the emergency department.
Asthma complicates up to 4% of pregnancies. Our objective was to compare emergency department (ED) visits for acute asthma among pregnant versus nonpregnant women. We performed a prospective cohort study, as part of the Multicenter Asthma Research Collaboration. ⋯ Pregnant women were equally likely to be admitted (24% versus 21%, p = 0.61) but less likely to be prescribed corticosteroids if sent home (38% versus 64%, p = 0.002). At 2-wk follow-up, pregnant women were 2.9 times more likely to report an ongoing exacerbation (95% CI, 1.2 to 6.8). Among women presenting to the ED with acute asthma, pregnant asthmatics are less likely to receive appropriate treatment with corticosteroids.
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Am. J. Respir. Crit. Care Med. · Sep 1999
The attributable mortality and costs of primary nosocomial bloodstream infections in the intensive care unit.
Primary nosocomial bloodstream infection (BSI) is a common occurrence in the intensive care unit (ICU) and is associated with a crude mortality of 31.5 to 82.4%. However, an accurate estimate of the attributable mortality has been limited because of confounding by severity of illness. We undertook this study to assess the attributable mortality and costs associated with an episode of BSI. ⋯ However, among survivors, the patients with nosocomial bloodstream infections did have excess length of stay (mean, 10 d; median, 5 d; p = 0.007) and increased direct costs (mean difference, $34,508; p = 0.008). After matching for severity of illness, we could not detect an association between primary nosocomial bloodstream infections and increased ICU mortality. We did find that primary nosocomial bloodstream infections increased ICU length of stay and costs.