Early alterations of the innate and adaptive immune statuses in sepsis according to the type of underlying infection.

INTRODUCTION: Although major changes of the immune system have been described in sepsis, it has never been studied whether these may differ in relation to the type of underlying infection or not. This was studied for the first time. METHODS: The statuses of the innate and adaptive immune systems were prospectively compared in 505 patients. Whole blood was sampled within less than 24 hours of advent of sepsis; white blood cells were stained with monoclonal antibodies and analyzed though a flow cytometer. RESULTS: Expression of HLA-DR was significantly decreased among patients with severe sepsis/shock due to acute pyelonephritis and intraabdominal infections compared with sepsis. The rate of apoptosis of natural killer (NK) cells differed significantly among patients with severe sepsis/shock due to ventilator-associated pneumonia (VAP) and hospital-acquired pneumonia (HAP) compared with sepsis. The rate of apoptosis of NKT cells differed significantly among patients with severe sepsis/shock due to acute pyelonephritis, primary bacteremia and VAP/HAP compared with sepsis. Regarding adaptive immunity, absolute counts of CD4-lymphocytes were significantly decreased among patients with severe sepsis/shock due to community-acquired pneumonia (CAP) and intraabdominal infections compared with sepsis. Absolute counts of B-lymphocytes were significantly decreased among patients with severe sepsis/shock due to CAP compared with sepsis. CONCLUSIONS: Major differences of the early statuses of the innate and adaptive immune systems exist between sepsis and severe sepsis/shock in relation to the underlying type of infection. These results may have a major impact on therapeutics.

The impact of the PAI-1 4G/5G polymorphism on the outcome of patients with ALI/ARDS.

INTRODUCTION: Increased levels of plasminogen activator inhibitor-1 (PAI-1) have been associated with worse outcome in ALI/ARDS. A single guanosine insertion/deletion (4G/5G) polymorphism in the promoter region of the PAI-1 gene, may play an important role in the regulation of PAI-1 expression. The objective of the study was to evaluate the effect of this polymorphism on the outcome of critically ill patients with ALI/ARDS. MATERIALS AND METHODS: 52 consecutive ventilated patients with ALI/ARDS were studied. Bronchoalveolar lavage was performed within 48 hours from diagnosis. Measurement of plasma and BALF PAI-1 activity and D-dimers levels, and 4G/5G genotyping of PAI-1 were carried out. The primary outcome was 28-day mortality, and secondary outcomes included organ dysfunction and ventilator-free days. RESULTS: 17 patients were homozygotes for the 4G allele. Severity scores were not different between subgroups upon study enrollment. 28-day mortality was 70.6% and 42.9% for the 4G-4G and the non-4G-4G patients, respectively (p=0.06). PAI-1 activity levels and D-dimer in plasma and BALF were not significantly different between the 4G-4G and the non-4G-4G subgroups. In the multivariate analysis, genotype 4G/4G was the only variable independently associated with 28-day mortality (Odds Ratio=9.95, 95% CI: 1.79-55.28, p=0.009). Furthermore, genotype 4G/4G and plasma PAI-1 activity levels were independently negatively associated with ventilator free days (p=0.033 and p=0.008, respectively). CONCLUSIONS: ALI/ARDS patients, homozygous for the 4G allele of the PAI-1 gene, experienced higher 28-day mortality. This genotype was associated with a reduction in the number of days of unassisted ventilation and was inversely associated with the number of days without organ failure.

Prognostic importance of increased plasma amino-terminal pro-brain natriuretic peptide levels in a large noncardiac, general intensive care unit population.

The present study aimed to determine whether amino-terminal pro-brain natriuretic peptide (NT-pro-BNP) predicts intensive care unit (ICU) mortality in a cohort of general, noncardiac, critically ill patients. To this end, a total of 233 consecutive mechanically ventilated patients (109 men) having a median age of 60 years and a wide range in admitting diagnoses, including medical (n = 118), surgical (n = 83), and multiple trauma (n = 32) cases were prospectively studied. Median Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment scores on ICU admission were 16 and 9, respectively. The study end point was ICU outcome. Blood samples were drawn on admission in the ICU and on postadmission days 1 and 2 to determine NT-pro-BNP levels. In a subgroup (n = 77), admission proinflammatory and anti-inflammatory cytokine levels, including TNF-alpha, IL-6, and IL-10, were also measured. Nonsurvivors (n = 98) had significantly higher NT-pro-BNP levels than survivors (n = 135) on admission in the ICU (2,074 vs. 283 pg/mL; P < 0.001), on day 1 (2,197 vs. 221 pg/mL; P < 0.001), and on day 2 (2,726 vs. 139 pg/mL; P < 0.001). Median values for TNF-alpha, IL-6, and IL-10 were 3.70, 131.57, and 111.88 pg/mL, respectively. Receiver operating characteristic analysis showed that the area under the receiver operating characteristic curve in predicting ICU mortality was 0.70 for APACHE II and 0.77 for admission NT-pro-BNP (P = 0.08). The cutoff in admission NT-pro-BNP that best predicted outcome was 941 pg/mL. Multiple logistic regression analysis revealed that APACHE II score (odds ratio, 1.06; P = 0.007) and the best cutoff point in admission NT-pro-BNP (odds ratio, 7.74; P < 0.001) independently predicted ICU mortality, even if cytokines were entered in the analysis. In conclusion, plasma NT-pro-BNP is frequently raised in noncardiac, mixed, critically ill patients, and nonsurvivors have consistently higher levels than survivors. Elevated admission NT-pro-BNP represents an independent predictor for poor ICU outcome in the presence of clinical severity scores.

Pleural effusion causing cardiac tamponade: report of two cases and review of the literature.

We report on two patients who developed large left-sided pleural effusions in association with hemodynamic compromise. In both cases transthoracic echocardiography demonstrated left ventricular diastolic collapse confirming our clinical suspicion of cardiac tamponade. Large-volume thoracentesis in the first case and thoracotomy with drainage of the pleural collection in the second case resulted in immediate hemodynamic improvement. Our report shows that large pleural effusions can result in impaired cardiac filling and a tamponade-like physiology. Thoracentesis in this setting can lead to rapid improvement of the hemodynamic profile.

Cytarabine-induced lung injury: case report.

We report the case of a 65-year-old male patient with acute myelogenous leukemia who developed severe respiratory failure after receiving cytarabine treatment. Chest radiograph showed bilateral alveolar infiltrates. He was intubated and underwent flexible bronchoscopy. An extensive diagnostic work-up revealed no evidence of infection. Steroids were added to empiric antibiotic treatment and the patient was successfully extubated in 5 days. Cytarabine-induced lung injury should be considered in the differential diagnosis of alveolar infiltrates in immunocompromised patients. If bronchoscopy fails to confirm an infectious cause, a short course of steroids must be tried, which probably leads to a favorable outcome.

Prediction of prolonged ventilatory support in blunt thoracic trauma patients.

OBJECTIVE: To identify predictors of prolonged (>7 days) mechanical ventilation (MV) in patients with blunt thoracic trauma. DESIGN: Prospective analysis of consecutive patients. SETTING: Adult intensive care unit (ICU) in a teaching, tertiary-care hospital. PATIENTS AND PARTICIPANTS: Sixty-nine patients (53 men, 16 women) with thoracic trauma having a median age of 35 (range 17-85) years and a median injury severity score (ISS) of 29 (range 14-41) were enrolled in the present study. Associated injuries included head-neck (77%), extremities (72%), external (67%), abdomen-pelvis (67%), and face (55%). INTERVENTIONS: Patient surveillance and data collection. MEASUREMENTS AND RESULTS: Thirty-three (48%) of the 69 patients required prolonged ventilatory support, ranging in duration from 8 to 38 (median 18) days. Logistic regression analysis revealed that advancing age (odds ratio=1.04, p=0.04), severity of head injury (odds ratio=1.92, p=0.008), and bilateral thoracic injuries (odds ratio=12.80, p<0.0001) were significant and independent predictors of long-lasting MV. In contrast, gender, injuries affecting the other body regions (face, abdomen-pelvis, extremities, and external), laparotomy in patients with abdominal injury, or PaO(2)/FIO(2) on admission in the ICU, were unrelated to prolonged MV. CONCLUSIONS: In thoracic trauma patients admitted in the ICU, prolonged mechanical ventilation was primarily determined by presence of bilateral chest injuries, age, and degree of neurotrauma. This information may help in planning the long-term care of such patients.