Early infectious acute respiratory distress syndrome is characterized by activation and proliferation of alveolar T-cells.

Acute respiratory distress syndrome (ARDS) in humans is characterized by the infiltration of polymorphonuclears in the alveolar spaces. However, the role of T-cells in ARDS is unknown. Our aim was to characterize the T-cell phenotype in bronchoalveolar lavage (BAL) during the early phase of acute lung infection(ALI)/ARDS-infected patients in comparison to a control group (CG). BAL lymphocyte phenotypes of two ALI, 16 ARDS, and eight CG were examined by flow cytometry. ALI/ARDS showed a significant increase in CD4 and CD8 T-cell activation as compared to CG. Moreover, a significant level of proliferation was observed using the Ki67 marker in ARDS patients as compared to controls (median): 37 versus 6 % for CD4 T-cells (p = 0.022) and 34 versus 2 % for CD8 T-cells (p = 0.009). In contrast, the percentage of T-regulatory cells and apoptotic T-cells were similar in both groups. Among costimulatory molecules, we observed an overexpression of CTLA-4/CD152 on CD4 T-cells in ALI/ARDS as compared to CG: 30 versus 7 %, respectively (p = 0.063). In further characterizing T-cell subsets expressing high levels of CD152, we found the presence of IL-17 secreting CD4 T-cells in ALI/ARDS. In humans, ALI/ARDS due to infection is associated with a high level of T-cell activation and proliferation, along with the presence of Th17 cells, which are known to attract polymorphonuclears.

Effect of different seated positions on lung volume and oxygenation in acute respiratory distress syndrome.

RATIONALE: Lung volume available for ventilation is markedly decreased during acute respiratory distress syndrome. Body positioning may contribute to increase lung volume and partial verticalization is simple to perform. This study evaluated whether verticalization had parallel effects on oxygenation and end expiratory lung volume (EELV). METHODS: Prospective multicenter study in 40 mechanically ventilated patients with ALI/ARDS in five university hospital MICUs. We evaluated four 45-min successive trunk position epochs (supine slightly elevated at 15°; semi recumbent with trunk elevated at 45°; seated with trunk elevated at 60° and legs down at 45°; back to supine). Arterial blood gases, EELV measured using the nitrogen washin/washout, and static compliance were measured. Responders were defined by a PaO2/FiO2 increase >20 % between supine and seated position. Results are median [25th-75th percentiles]. RESULTS: With median PEEP = 10 cmH2O, verticalization increased lung volume but only responders (13 patients, 32 %) had a significant increase in EELV/PBW (predicted body weight) compared to baseline. This increase persisted at least partially when patients were positioned back to supine. Responders had a lower EELV/PBW supine [14 mL/kg (13-15) vs. 18 mL/kg (15-27) (p = 0.005)] and a lower compliance [30 mL/cmH2O (22-38) vs. 42 (30-46) (p = 0.01)] than non-responders. Strain decreased with verticalization for responders. EELV/PBW increase and PaO2/FiO2 increase were not correlated. DISCUSSION: Verticalization is easily achieved and improves oxygenation in approximately 32 % of the patients together with an increase in EELV. Nonetheless, effect of verticalization on EELV/PBW is not predictable by PaO2/FiO2 increase, its monitoring may be helpful for strain optimization.

PEEP-induced changes in lung volume in acute respiratory distress syndrome. Two methods to estimate alveolar recruitment.

PURPOSE: Lung volumes, especially functional residual capacity (FRC), are decreased in acute respiratory distress syndrome (ARDS). Positive end-expiratory pressure (PEEP) contributes to increased end-expiratory lung volume (EELV) and to improved oxygenation, but differentiating recruitment of previously nonaerated lung units from distension of previously open lung units remains difficult. This study evaluated simple methods derived from bedside EELV measurements to assess PEEP-induced lung recruitment while monitoring strain. METHODS: Prospective multicenter study in 30 mechanically ventilated patients with ARDS in five university hospital ICUs. Two PEEP levels were studied, each for 45 min, and EELV (nitrogen washout/washin technique) was measured at both levels, with the difference (Δ) reflecting PEEP-induced lung volume changes. Alveolar recruitment was measured using pressure-volume (PV) curves. High and low recruiters were separated based on median recruitment at high PEEP. Minimum predicted increase in lung volume computed as the product of ΔPEEP by static compliance was subtracted from ΔEELV as an independent estimate of recruitment. Estimated and measured recruitments were compared. Strain induced by PEEP was also calculated from the same measurements. RESULTS: FRC was 31 ± 11% of predicted. Median [25th-75th percentiles] PEEP-induced recruitment was 272 [187-355] mL. Estimated recruitment correlated with recruited volume measured on PV curves (ρ = 0.68), with a slope close to identity. The ΔEELV/FRC ratio differentiated high from low recruiters (110 [76-135] vs. 55 [23-70]%, p = 0.001). Strain increase due to PEEP was larger in high recruiters (p = 0.002). CONCLUSION: PEEP-induced recruitment and strain can be assessed at the bedside using EELV measurement. We describe two bedside methods for predicting low or high alveolar recruitment during ARDS.

Impact of an intervention designed to improve the documentation of the reassessment of antibiotic therapies in an intensive care unit.

OBJECTIVES: The study objectives were: (i) to design an intervention to improve the written documentation of empiric antibiotic prescriptions' reassessment; (ii) and to assess the impact of this intervention on the quality of prescriptions. PATIENTS AND METHODS: A prospective before and after 7-month intervention study in a medical ICU in a French teaching hospital, using interrupted time-series analysis. The intervention was made to improve the documentation of four process measures in medical records: antibiotic plan, reviewing the diagnosis, adapting to positive microbiological results, and IV-per os switch. RESULTS: One hundred and fourteen antibiotic prescriptions were assessed, 62 before and 52 after the intervention. The reassessment of antibiotic prescriptions was more often documented in the ICU after the intervention (P=0.03 for sudden change). The prevalence of appropriate antibiotic prescriptions was not statistically different before and after the intervention, either for sudden change and/or linear trend. CONCLUSION: A better documentation of antibiotic prescriptions' reassessment was achieved in this ICU, but it did not improve the quality of antibiotic prescriptions.

Impact of an assisted reassessment of antibiotic therapies on the quality of prescriptions in an intensive care unit.

OBJECTIVES: The study's objective was to assess the impact of a professional multifaceted intervention designed to improve the quality of inpatient empirical therapeutic antibiotic courses at the time of their reassessment, i.e. 24 to 96 hours after treatment initiation. DESIGN: We conducted a 5-month prospective pre- and post-intervention study in a medical Intensive Care Unit (ICU) in a teaching hospital, using time-series analysis. The intervention was a multifaceted professional intervention combining systematic 3-weekly visits of an infectious diseases specialist to discuss all antibiotic therapies, interactive teaching courses, and daily contact with a microbiologist. RESULTS: Eighty-one antibiotic prescriptions were assessed, 37 before and 44 after the intervention. The prevalence of adequate antibiotic prescriptions was high and not statistically different before and after the intervention (73% vs. 80%, P=0.31), both for sudden change (P=0.67) and linear trend (P=0.055), using interrupted time-series analysis. The intervention triggered a more frequent reassessment of the diagnosis between day 2 and day 4 (11% vs. 32%, P=0.02) and slightly improved the adaptation of antibiotic therapies to positive microbiology (25% before vs. 50% after, P=0.18). CONCLUSIONS: Our multifaceted intervention may have improved the quality of antibiotic therapies around day 3 of prescription, but the difference did not reach statistical significance, possibly because of a ceiling effect.

[Urinary pneumococcal or Legionella antigen detection tests and low-spectrum antibiotic therapy for community-acquired pneumonia]. / Antigènuries pneumocoque ou Legionella et antibiothérapie à spectre restreint au cours des pneumonies aiguës communautaires.

UNLABELLED: We performed urinary antigen tests for pneumococcus and Legionella for patients with community-acquired pneumonia (CAP), to prescribe a documented antibiotic therapy. We report the efficiency of low-spectrum antibiotic treatment, illustrating the inappropriateness of bacteriological respiratory sampling. PATIENTS AND METHODS: Patients with CAP were enrolled from three different units; the pneumonia severity index was used to assess the disease. Respiratory samples were also listed. Low-spectrum antibiotic therapy was amoxicillin for pneumococcal infection, and macrolides or non-anti-pneumococcal fluoroquinolone for legionellosis. RESULTS: Six hundred and seventy-five CAP were diagnosed during the study period,, 150 with positive urinary antigen tests (23%), among which 108 pneumococcal infections (73%), 40 legionellosis (26%), and two mixed infections. The pneumonia severity index was 106+/-38. Amoxicillin was prescribed in 108 cases, fluoroquinolone in 24 cases, macrolide in 18 cases. The outcome was favourable for 138 patients (92%). Eighty three respiratory samples allowed identification of a bacterium for 58 patients (39%), among which 24 strains were not in the antibiotic spectrum: Haemophilus influenzae and Pseudmomonas aeruginosa in six cases, Staphylococcus aureus in five cases, Klebsiella pneumoniae in two cases, and another Gram negative bacillus in five cases. These strains were resistant in vitro to the prescribed treatment in 19/24 cases (79%). One out of 12 patients who died had a respiratory sample positive for Enterobacter spp strain resistant to the ongoing antibiotic treatment. CONCLUSION: The low-spectrum antibiotic therapy based on urinary antigen tests is efficient, and demonstrates respiratory tract colonisation with bacteriological strains usually considered as pathogenic.

Enhanced T-cell apoptosis in human septic shock is associated with alteration of the costimulatory pathway.

T-cell apoptosis during septic shock (SS) has been associated with deleterious outcome, but the mechanisms of apoptosis are not well understood. As T-cells are not infected in bacterial infection, our hypothesis was that deleterious interactions between lymphocytes and monocytes could be involved. This is a cross-sectional study of 27 patients presenting with community-acquired SS, 23 infected patients without SS and 18 controls. Cytofluorometric techniques were used to study apoptosis, the costimulatory pathway and cytokine synthesis. Apoptosis was increased in SS compared to infected patients without SS and controls: the median values were 18, 2 and 3%, respectively, for CD4(+) T-cells (P < 0.001), and 12, 5 and 2%, respectively, for CD8(+) T-cells (P < 0.001). Patients with SS exhibited significant CD152 over-expression on T-cells, while CD86 expression was decreased on monocytes (P = 0.004). The synthesis of interleukin-2 was decreased in patients with SS compared to the other groups, while secretions of interferon-gamma and TNF-alpha were not altered. Ten surviving patients with SS showed a trend towards the normalisation of these parameters on day 7. In SS, T-cell apoptosis is related, at least in part, to the alteration of the costimulatory pathway, which, in turn, leads to significant modification of the cytokine network.

[Acute airway obstruction during chemotherapy-induced agranulocytosis with fever]. / Moules bronchiques au cours d'une agranulocytose fébrile post-chimiothérapie.

Acute airway obstruction caused by mucoid impaction can cause sometimes life-threatening respiratory distress. Bronchial plugging is usually observed in subjects with chronic diseases such as asthma, allergic bronchopulmonary aspergillosis, or cystic fibrosis. In children, it can be related to heart failure. Acute airway obstruction in a patient without a chronic respiratory disease is exceptional. We report the case of a patient who developed bronchial plugs obstructing the bronchi during a period of agranulocytosis induced by chemotherapy. The patient experienced acute respiratory distress with asphyxia. The plugs were composed of fibrin and required several fibroscopic procedures for clearance. To our knowledge, this is the first case report of acute airway obstruction by plugging during a period of agranulocytosis.

Consensual treatment of plasmodium falciparum malaria does not lead to adequate quinine blood concentrations.

Since 1996, we have a common protocol in the Infectious Diseases Department and the Intensive Care Unit for the administration of quinine in case of Plasmodium falciparum malaria. Patients were classified as uncomplicated form of malaria (UFM) or severe form of malaria (SFM) according to WHO criteria, adding parasitemia >5% as a criteria of SFM. Treatment of SFM should consist of a 4 h infusion of 16 mg/kg quinine-base loading dose, followed by 8 mg/kg every 8 h. Patients with UFM receive quinine-base, 8 mg/kg every 8 h. A therapeutic index of 10-15 mg/l was considered adequate. Hypoglycemia and cardiotoxicity were the two main adverse effects of quinine to be investigated. In order to verify that these modalities for quinine administration are associated with adequate quinine blood concentrations, we have reviewed the pharmacological data and the occurrence of adverse effects. Between April 1996 and December 2000, 95 patients were hospitalised: 25 with SFM and 70 with UFM: 78/95 patients (82%) received adequate treatment and 26/95 (28%) of the patients presented an overdosage of quinine. Six severe adverse effects were observed, even in case of adequate quinine administration. Consensual treatment of malaria does not confer adequate quinine blood concentrations, and toxic effects are still common.

Estimating cardiac filling pressure in mechanically ventilated patients with hyperinflation.

OBJECTIVE: When positive end-expiratory pressure (PEEP) is applied, the intracavitary left ventricular end-diastolic pressure (LVEDP) exceeds the LV filling pressure because pericardial pressure exceeds 0 at end-expiration. Under those conditions, the LV filling pressure is itself better reflected by the transmural LVEDP (tLVEDP) (LVEDP minus pericardial pressure). By extension, end-expiratory pulmonary artery occlusion pressure (eePAOP), as an estimate of end-expiratory LVEDP, overestimates LV filling pressure when pericardial pressure is >0, because it occurs when PEEP is present. We hypothesized that LV filling pressure could be measured from eePAOP by also knowing the proportional transmission of alveolar pressure to pulmonary vessels calculated as index of transmission = (end-inspiratory PAOP--eePAOP)/(plateau pressure--total PEEP). We calculated transmural pulmonary artery occlusion pressure (tPAOP) with this equation: tPAOP = eePAOP--(index of transmission x total PEEP). We compared tPAOP with airway disconnection nadir PAOP measured during rapid airway disconnection in subjects undergoing PEEP with and without evidence of dynamic pulmonary hyperinflation. DESIGN: Prospective study. SETTING: Medical intensive care unit of a university hospital. PATIENTS: We studied 107 patients mechanically ventilated with PEEP for acute respiratory failure. Patients without dynamic pulmonary hyperinflation (group A; n = 58) were analyzed separately from patients with dynamic pulmonary hyperinflation (group B; n = 49). INTERVENTION: Transient airway disconnection. MEASUREMENTS AND MAIN RESULTS: In group A, tPAOP (8.5+/-6.0 mm Hg) and nadir PAOP (8.6+/-6.0 mm Hg) did not differ from each other but were lower than eePAOP (12.4+/-5.6 mm Hg; p < .05). The agreement between tPAOP and nadir PAOP was good (bias, 0.15 mm Hg; limits of agreement, -1.5-1.8 mm Hg). In group B, tPAOP (9.7+/-5.4 mm Hg) was lower than both nadir PAOP and eePAOP (12.1+/-5.4 and 13.9+/-5.2 mm Hg, respectively; p < .05 for both comparisons). The agreement between tPAOP and nadir PAOP was poor (bias, 2.3 mm Hg; limits of agreement, -0.2-4.8 mm Hg). CONCLUSIONS: Indexing the transmission of proportional alveolar pressure to PAOP in the estimation of LV filling pressure is equivalent to the nadir method in patients without dynamic pulmonary hyperinflation and may be more reliable than the nadir PAOP method in patients with dynamic pulmonary hyperinflation.

[Systematic infection consultation in the intensive care unit. Impact of short-term antibiotic use]. / Consultation systématique d'infectiologie en réanimation médicale. Impact à court terme sur la consommation antibiotique.

OBJECTIVES: Multiresistant bacteria are regularly isolated in nosocomial infections occurring in intensive care units due to wide use of antibiotics. We evaluated the impact of systematic infectiology consultations on the quality of antibiotic prescriptions in an intensive care unit. PATIENTS AND METHODS: Infectiology consultations (3 per week) were initiated mid February 1999. The infectiologist gave oral advice to be implemented (or not) by the intensive care unit according to ongoing therapeutic options. The hospital pharmacy recorded antibiotic use for March and April 1999 for comparison with use recorded in 1998 for a similar period. We retrospectively reviewed the files of patients hospitalized during these periods and who had received antibiotics to determine the modalities of antibiotic use. The 4 antibiotics used for the longest period for each patient were recorded. RESULTS: Thirty-one patients in 1999 and 30 in 1998 were given antibiotics. The SAPS score was similar for the two groups. Mean duration of antibiotic treatment was lower during the March-April 1999 period than during the corresponding period in 1998: 13 +/- 9 days/patient versus 23 +/- 21 days/patient respectively, p = 0.037. In 1998, there were 596 antibiotic-days and in 1999 there were 455 (-24%). The cost of antibiotic therapy in 1998 was 70,342 FrF compared with 56,804 FrF in 1999 (-19%). CONCLUSION: Infectiology consultation, in association with the opinion of the intensive care physician, is a simple way to limit antibiotic use.