To assess the initial serum levels of lipids and lipoproteins and their correlations with the clinical outcome for patients with severe sepsis. The ability of high-density lipoprotein (HDL) to attenuate lipopolysaccharide (LPS)–induced cytokine production was also examined in vitro. Prospective, observational cohort study. Medical intensive care unit (ICU) of a tertiary-level university hospital. Sixty-three consecutive patients with severe sepsis. Blood samples were drawn within the first day of severe sepsis and the subsequent 14 days. Clinical outcome, including length of ICU stay, infection subsequent to hospital stay, and death, were monitored prospectively. Compared with the survivors, patients who died within 30 days had significantly lower levels of HDL cholesterol and apolipoprotein A-I during the first 4 days of severe sepsis. On day 1, HDL cholesterol levels correlated inversely with interleukin-6 (r = −0.72; p < .01) and tumor necrosis factor (TNF)-α (r = −0.70; p < .01) concentrations. Not only the overall and sepsis-attributable 30-day mortality rates but also the risk of prolonged ICU stay (>7 days) and the hospital-acquired infection rate were increased among patients with day 1 levels of HDL cholesterol of <20 mg/dL and apolipoprotein A-I of <100 mg/dL. Multivariate analysis identified an HDL cholesterol level of <20 mg/dL on day 1 (odds ratio, 12.92; 95% confidence interval, 2.73–61.29) and Acute Physiology and Chronic Health Evaluation II score (odds ratio, 1.15; 95% confidence interval, 1.04–1.26) as independent predictors of the overall 30-day mortality rate. In human macrophages, LPS-induced TNF-α release was attenuated by incremental doses of HDL cholesterol added simultaneously (p < .01). However, HDL failed to suppress LPS-induced TNF-α production when administered after macrophages were exposed to LPS. A low HDL cholesterol level on day 1 of severe sepsis is significantly associated with an increase in mortality and adverse clinical outcomes. In cultured macrophages, HDL can attenuate LPS-induced TNF-α production only if added concomitantly with, but not after, LPS exposure.

Introduction: Tracheostomy is frequently performed in critically ill patients for prolonged intubation. However, the optimal timing of tracheostomy, and its impact on weaning from mechanical ventilation and outcomes in critically ill patients who require mechanical ventilation remain controversial. Methods: The medical records of patients who underwent tracheostomy in the medical intensive care unit (ICU) of a tertiary medical centre from July 1998 to June 2001 were reviewed. Clinical characteristics, length of stay in the ICU, rates of post-tracheostomy pneumonia, weaning from mechanical ventilation and mortality rates were analyzed. Results: A total of 163 patients (93 men and 70 women) were included; their mean age was 70 years. Patients were classified into two groups: successful weaning (n = 78) and failure to wean (n = 85). Shorter intubation periods (P = 0.02), length of ICU stay (P = 0.001) and post-tracheostomy ICU stay (P = 0.005) were noted in patients in the successful weaning group. Patients who underwent tracheostomy more than 3 weeks after intubation had higher ICU mortality rates and rates of weaning failure. The length of intubation correlated with the length of ICU stay in the successful weaning group (r = 0.70; P < 0.001). Multivariate analysis revealed that tracheostomy after 3 weeks of intubation, poor oxygenation before tracheostomy (arterial oxygen tension/fractional inspired oxygen ratio <250) and occurrence of nosocomial pneumonia after tracheostomy were independent predictors of weaning failure. Conclusion: The study suggests that tracheostomy after 21 days of intubation is associated with a higher rate of failure to wean from mechanical ventilation, longer ICU stay and higher ICU mortality.

There has been increasing evidence that angiotensin II may play an important role in the pathogenesis and in the evolution of acute lung injury. It was therefore hypothesized that polymorphisms of the angiotensin-converting enzyme gene affects the risk and outcome of acute respiratory distress syndrome (ARDS). Prospective, observational study. The ARDS group consisted of 101 patients treated at the medical intensive care unit; the control groups consisted of 138 “at-risk” patients treated at the medical intensive care unit due to acute respiratory failure but did not meet the ARDS criteria throughout the hospital course, and 210 non–at-risk subjects. None. The ARDS patients and control subjects were genotyped for the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme gene. Association of the polymorphism and the risk and the outcome of ARDS was analyzed. There was no significant difference in the frequencies of the genotypes between the ARDS, at-risk, and non–at-risk groups. The 28-day mortality rates were significantly different between the three angiotensin-converting enzyme genotypes (42%, 65%, and 75% for II, ID, and DD, respectively; p = .036). Survival analysis showed that the II genotype favorably affected 28-day survival (hazard ratio, 0.46; 95% confidence interval, 0.26–0.81; p = .007), whereas ARDS caused by hospital-acquired pneumonia had a negative effect (hazard ratio, 2.34; 95% confidence interval, 1.25–4.40; p = .008). The II genotype (hazard ratio, 0.53; 95% confidence interval, 0.32–0.87; p = .012) and ARDS caused by hospital-acquired pneumonia (hazard ratio, 2.13; 95% confidence interval, 1.24–3.68; p = .006) were also significant prognostic factors for the in-hospital mortality. The angiotensin-converting enzyme I/D polymorphism is a significant prognostic factor for the outcome of ARDS. Patients with the II genotype have a significantly better chance of survival. This study did not show an increased risk for ARDS in Chinese patients with the D allele.

Sepsis-related mortality has been found increased in RAG-1 knockout mice. However, in patients admitted to medical intensive care units, it is unknown whether severe lymphocyte depletion at admission is associated with increased interleukin (IL)-7 and IL-15 levels in circulation, and increased mortality. We prospectively enrolled 92 patients who were admitted to medical intensive care units for severe sepsis or septic shock. At admission, 24 patients (26.1%) had severe lymphopenia, defined as lymphocyte counts of less than 0.5 × 10³/μL. Severe lymphopenia was associated with significantly higher plasma levels of tumor necrosis factor α, IL-6, IL-8, and IL-10 and was also independently associated with 28-day mortality (adjusted hazard ratio, 3.532; 95% confidence interval, 1.482−8.416; P = 0.004). The levels of plasma IL-15, but not IL-7, were increased modestly in patients with severe lymphopenia compared with those without (median, 12.2 vs. 6.4 pg/mL; P = 0.005). The elevated plasma IL-15 levels were contrarily associated with significantly decreased B-cell lymphoma 2 mRNA expression in peripheral blood mononuclear cells. In conclusion, severe lymphopenia was associated with increased mortality in patients with severe sepsis. We found that patients with sepsis with severe lymphopenia had down-regulated B-cell lymphoma 2 mRNA expression in peripheral blood mononuclear cells, despite increased plasma IL-15 concentrations. Whether IL-7 and IL-15 are insufficient in patients with severe lymphopenia during severe sepsis warrants further investigations.