Available evidence suggests that both hydrostatic and osmotic forces are important in the development of acute respiratory distress syndrome (ARDS) or, more broadly, acute lung injury (ALI). More than 80% of ARDS patients in a large-scale randomized controlled trial (RCT) exhibited, at least intermittently, pulmonary artery wedge pressures (PAWP) above 18 mmHg. Retrospective analyses have shown that PAWP elevation is associated with increased mortality. Reduction in serum total protein (STP) has been shown, in a recent retrospective analysis of data from a sepsis patient population with a high frequency of ARDS, to be highly predictive of positive fluid balance, weight gain, development of ARDS, prolonged mechanical ventilation, and mortality. These findings suggest that therapy with diuretics and colloids might be of benefit in the prevention or treatment of ALI. A prospective RCT was designed and conducted to evaluate combination therapy with furosemide and albumin over a 5-day period in 37 ALI patients. Both mean serum albumin and mean STP increased promptly and substantially in furosemide + albumin recipients. The furosemide + albumin group also achieved a mean weight loss of 10 kg by the end of the treatment phase, and their weight loss exceeded that of placebo patients throughout. Hemodynamics improved in the treatment group during the 5-day protocol. Oxygenation, as assessed by the ratio between the fraction of inspired oxygen and the partial pressure of oxygen in arterial blood (PaO2/FiO2), was significantly higher within 24 h after commencement of treatment in the furosemide + albumin than the placebo group. No clinically important adverse effects of furosemide + albumin therapy were encountered. These results provide evidence that combined therapy with furosemide and albumin is effective in augmenting serum albumin and STP levels, promoting weight loss, and improving oxygenation and longer-term hemodynamic stability. Although mortality did not differ between groups, the RCT showed a trend toward reduced duration of mechanical ventilation and length of stay in the intensive care unit in patients receiving furosemide + albumin. The findings of the RCT further highlight the importance of both hydrostatic and osmotic forces in hypoxemic respiratory failure, a subject that requires further investigation.

Background—Left ventricular (LV) dysfunction is common in children infected with the human immunodeficiency virus (HIV), but its clinical importance is unclear. Our objective was to determine whether abnormalities of LV structure and function independently predict all-cause mortality in HIV-infected children. Methods and Results—Baseline echocardiograms were obtained on 193 children with vertically transmitted HIV infection (median age, 2.1 years). Children were followed up for a median of 5 years. Cox regression was used to identify measures of LV structure and function predictive of mortality after adjustment for other important demographic and baseline clinical risk factors. The time course of cardiac variables before mortality was also examined. The 5-year cumulative survival was 64%. Mortality was higher in children who, at baseline, had depressed LV fractional shortening (FS) or contractility; increased LV dimension, thickness, mass, or wall stress; or increased heart rate or blood pressure (P≤0.02 for each). Decreased LV FS (P<0.001) and increased wall thickness (P=0.004) were also predictive of increased mortality after adjustment for CD4 count (P<0.001), clinical center (P<0.001), and encephalopathy (P<0.001). FS showed abnormalities for up to 3 years before death, whereas wall thickness identified a population at risk only 18 to 24 months before death. Conclusions—Depressed LV FS and increased wall thickness are risk factors for mortality in HIV-infected children independent of depressed CD4 cell count and neurological disease. FS may be useful as a long-term predictor and wall thickness as a short-term predictor of mortality.

Background Peripheral blood CD4+ and CD8+ T cells, CD19+/20+ B cells, and serum Igs are known to be altered by the progression of pediatric HIV-1 infection, but their evaluation as predictors of survival needs further definition. Objective To determine the natural history of these immune factors and their importance in predicting survival, we studied 298 HIV-1 vertically infected (HIV-1+) children over a 5-year period. Methods These immune factors and serum HIV-1 RNA levels were measured in two groups: (1) a birth cohort of children enrolled up to age 28 days postnatally, including 93 HIV-1+ and 463 HIV-1 uninfected infants (HIV-1−), and (2) an older cohort of 205 HIV-1+ children enrolled after the age of 28 days, who were classified as survivors or nonsurvivors. Results In the birth cohort HIV-1+ children had significantly lower CD4+ T-cell counts, higher CD8+ T-cell counts, and lower CD19+/20+ B-cell counts and higher IgG, IgA, and IgM levels than HIV-1− children. In the older cohort survivors had significantly higher CD4+ and CD8+ T-cell and CD19+/CD20+ B-cell counts and higher IgG, lower IgA, and lower IgM levels than did nonsurvivors. In univariable analysis factors affecting survival in the older cohort were baseline CD4+ and CD8+ T-cell and CD19+/20+ B-cell counts and IgG and HIV-1 RNA levels (all P < .05). In multivariable analysis high baseline CD4+ T-cell count and low baseline HIV-1 RNA load remained important. Conclusion The longitudinal mean profiles of CD4 and CD8 T-cell and CD19/20 B-cell counts and serum IgG levels helped to describe the natural progression of HIV-1 disease in children. However, only baseline CD4 T-cell count independently predicted survival.predicted survival.