Objective-The coagulation and inflammatory cascades may be linked in the pathogenesis of acute lung injury and acute respiratory distress syndrome. However, direct evidence for the contribution of abnormalities in coagulation and fibrinolysis proteins to outcomes in patients with acute lung injury/acute respiratory distress syndrome is lacking.Design-Retrospective measurement of plasma levels of protein C and plasminogen activator inhibitor-1 in plasma samples that were collected prospectively as part of a large multicenter clinical trial. The primary outcome was hospital mortality. To evaluate the potential additive value of abnormalities of these biomarkers, the excess relative risk of death was calculated for each combination of quartiles of protein-C and plasminogen activator inhibitor-1 levels. Setting-Ten university medical centers.Patients-The study included 779 patients from a multicenter clinical trial of a protective ventilatory strategy in acute lung injury/acute respiratory distress syndrome and 99 patients with acute cardiogenic pulmonary edema, as well as ten normal controls. Measurements and MainResults-Compared with plasma from controls and patients with acute cardiogenic pulmonary edema, baseline protein-C levels were low and baseline plasminogen activator inhibitor-1 levels were elevated in acute lung injury/acute respiratory distress syndrome. By multivariate analysis, lower protein C and higher plasminogen activator inhibitor-1 were strong independent predictors of mortality, and ventilator-free and organ-failure-free days. Plasminogen activator inhibitor-1 and protein C had a synergistic interaction for the risk of death. Conclusions-Early acute lung injury/acute respiratory distress syndrome is characterized by decreased plasma levels of protein C and increased plasma levels of plasminogen activator inhibitor-1 that are independent risk factors for mortality and adverse clinical outcomes. Measurement of plasminogen activator inhibitor-1 and protein-C levels may be useful to identify those at highest risk of adverse clinical outcomes for the development of new therapies. NIH Public Access Keywordsacute respiratory distress syndrome; protein C; plasminogen activator inhibitor-1; coagulation; fibrinolysis Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are life-threatening disorders characterized by severe inflammation in the lungs and frequent occurrence of multiple organ failure (1). Despite numerous randomized controlled trials of therapies aimed at modulating the inflammatory response in ALI/ARDS (2), the only therapy that has been proven to reduce mortality is a protective ventilatory strategy (3). Although mortality from ALI/ARDS has declined in clinical trials, epidemiologic studies that include all patients with ALI/ARDS still report mortality rates >50% (4). Insight into the pathophysiological derangements that characterize early clinical ALI/ARDS may help to guide the development of new therapies for this devastating disorder.The degree of alterations ...

The incidence of systemic Candida infections in patients requiring intensive care has increased substantially in recent years as a result of a combination of factors. More patients with severe underlying disease or immunosuppression from anti-neoplastic or anti-rejection chemotherapy and at risk from fungal infection are now admitted to the ICU. Improvements in supportive medical and surgical care have led to many patients who would previously have died as a result of trauma or disease surviving to receive intensive care. Moreover, some therapeutic interventions used in the ICU, most notably broad-spectrum antibiotics and intravascular catheters, are also associated with increased risks of candidiasis. Systemic Candida infections are associated with a high morbidity and mortality, but remain difficult to diagnose and ICU staff need to be acutely aware of this often insidious pathogen. A number of studies have identified risk factors for systemic Candida infection which may be used to identify those at highest risk. Such patients may be potential candidates for early, presumptive therapy. Here we review the epidemiology, pathogenesis, morbidity and mortality of systemic Candida infections in the ICU setting, and examine predisposing risk factors. Antifungal treatment, including the use of amphotericin B, flucytosine and fluconazole, and the roles of early presumptive therapy and prophylaxis, is also reviewed.

Pulmonary edema may be classified as increased hydrostatic pressure edema, permeability edema with diffuse alveolar damage (DAD), permeability edema without DAD, or mixed edema. Pulmonary edema has variable manifestations. Postobstructive pulmonary edema typically manifests radiologically as septal lines, peribronchial cuffing, and, in more severe cases, central alveolar edema. Pulmonary edema with chronic pulmonary embolism manifests as sharply demarcated areas of increased ground-glass attenuation. Pulmonary edema with veno-occlusive disease manifests as large pulmonary arteries, diffuse interstitial edema with numerous Kerley lines, peribronchial cuffing, and a dilated right ventricle. Stage 1 near drowning pulmonary edema manifests as Kerley lines, peribronchial cuffing, and patchy, perihilar alveolar areas of airspace consolidation; stage 2 and 3 lesions are radiologically nonspecific. Pulmonary edema following administration of cytokines demonstrates bilateral, symmetric interstitial edema with thickened septal lines. High-altitude pulmonary edema usually manifests as central interstitial edema associated with peribronchial cuffing, ill-defined vessels, and patchy airspace consolidation. Neurogenic pulmonary edema manifests as bilateral, rather homogeneous airspace consolidations that predominate at the apices in about 50% of cases. Reperfusion pulmonary edema usually demonstrates heterogeneous airspace consolidations that predominate in the areas distal to the recanalized vessels. Postreduction pulmonary edema manifests as mild airspace consolidation involving the ipsilateral lung, whereas pulmonary edema due to air embolism initially demonstrates interstitial edema followed by bilateral, peripheral alveolar areas of increased opacity that predominate at the lung bases. Familiarity with the spectrum of radiologic findings in pulmonary edema from various causes will often help narrow the differential diagnosis.Abbreviations: ARDS = adult respiratory distress syndrome, DAD = diffuse alveolar damage and the Institute of Diagnostic Radiology, Inselspital, Bern, Switzerland (P.V.). Recipient of a Certificate of Merit award for a scientific exhibit at the 1998 RSNA scientific assembly.

In a randomized, evaluator-blind, multicenter trial, we compared cefepime (2 g three times a day) with imipenem-cilastatin (500 mg four times a day) for the treatment of nosocomial pneumonia in 281 intensive care unit patients from 13 centers in six European countries. Of 209 patients eligible for per-protocol analysis of efficacy, favorable clinical responses were achieved in 76 of 108 (70%) patients treated with cefepime and 75 of 101 (74%) patients treated with imipenem-cilastatin. The 95% confidence interval (CI) for the difference between these response rates (؊16 to 8%) failed to exclude the predefined lower limit for noninferiority of ؊15%. In addition, therapy of pneumonia caused by an organism producing an extendedspectrum ␤-lactamase (ESBL) failed in 4 of 13 patients in the cefepime group but in none of 10 patients in the imipenem group. However, the clinical efficacies of both treatments appeared to be similar in a secondary intent-to-treat analysis (95% CI for difference, ؊9 to 14%) and a multivariate analysis (95% CI for odds ratio, 0.47 to 1.75). Furthermore, the all-cause 30-day mortality rates were 28 of 108 (26%) patients in the cefepime group and 19 of 101 (19%) patients in the imipenem group (P ‫؍‬ 0.25). Rates of documented or presumed microbiological eradication of the causative organism were similar with cefepime (61%) and imipenem-cilastatin (54%) (95% CI, ؊23 to 8%). Primary or secondary resistance of Pseudomonas aeruginosa was detected in 19% of the patients treated with cefepime and 44% of the patients treated with imipenem-cilastatin (P ‫؍‬ 0.05). Adverse events were reported in 71 of 138 (51%) and 62 of 141 (44%) patients eligible for safety analysis in the cefepime and imipenem groups, respectively (P ‫؍‬ 0.23). Although the primary end point for this study does not exclude the possibility that cefepime was inferior to imipenem, some secondary analyses showed that the two regimens had comparable clinical and microbiological efficacies. Cefepime appeared to be less active against organisms producing an ESBL, but primary and secondary resistance to imipenem was more common for P. aeruginosa. Selection of a single agent for therapy of nosocomial pneumonia should be guided by local resistance patterns.

Summary:Purpose: Refractory status epilepticus (RSE) is a critical medical condition with high mortality. Although propofol (PRO) is considered an alternative treatment to barbiturates for the management of RSE, only limited data are available. The aim of this study was to assess PRO effectiveness in patients with RSE.Methods: We retrospectively considered all consecutive patients with RSE admitted to the medical intensive care unit (ICU) between 1997 and 2002 treated with PRO for induction of EEGmonitored burst suppression. Subjects with anoxic encephalopathy showing pathological N20 on somatosensory evoked potentials were excluded.Results: We studied 31 RSE episodes in 27 adults (16 men, 11 women; median age, 41.5 years). All patients received PRO, and six also subsequently thiopental (THP). Clonazepam (CZP) was administered with PRO, and other antiepileptic drugs (AEDs) concomitant with PRO and THP. RSE was successfully treated with PRO in 21 (67%) episodes and with THP after PRO in three (10%). Median PRO injection rate was 4.8 mg/kg/h (range, 2.1-13), median duration of PRO treatment was 3 days (range, 1-9), and median duration of ICU stay was 7 days (range, 2-42). In 24 episodes in which the patient survived, shivering after general anesthesia was seen in 10 episodes, transient dystonia and hyperlipemia in one each, and mild neuropsychological impairment in five. The seven deaths were not directly related to PRO use.Conclusions: PRO administered with CZP was effective in controlling most of RSE episodes, without major adverse effects. In this setting, PRO may therefore represent a valuable alternative to barbiturates. A randomized trial with these drug classes could definitively assess their respective role in RSE treatment.