The Role of Natural Killer Cells in Sepsis

Severe sepsis and septic shock are still deadly conditions urging to develop novel therapies. A better understanding of the complex modifications of the immune system of septic patients is needed for the development of innovative immunointerventions. Natural killer (NK) cells are characterized as CD3−NKp46+CD56+ cells that can be cytotoxic and/or produce high amounts of cytokines such as IFN-γ. NK cells are also engaged in crosstalks with other immune cells, such as dendritic cells, macrophages, and neutrophils. During the early stage of septic shock, NK cells may play a key role in the promotion of the systemic inflammation, as suggested in mice models. Alternatively, at a later stage, NK cells-acquired dysfunction could favor nosocomial infections and mortality. Standardized biological tools defining patients' NK cell status during the different stages of sepsis are mandatory to guide potential immuno-interventions. Herein, we review the potential role of NK cells during severe sepsis and septic shock

Influence of support on intra-abdominal pressure, hepatic kinetics of indocyanine green and extravascular lung water during prone positioning in patients with ARDS: a randomized crossover study

INTRODUCTION: Prone positioning (PP) on an air-cushioned mattress is associated with a limited increase in intra-abdominal pressure (IAP) and an absence of organ dysfunction. The respective influence of posture by itself and the type of mattress on these limited modifications during the PP procedure remains unclear. The aim of this study was to evaluate whether the type of support modifies IAP, extravascular lung water (EVLW) and the plasma disappearance rate of indocyanine green (PDR(ICG)) during PP. METHODS: A prospective, randomized, crossover study of 20 patients with acute respiratory distress syndrome (ARDS) was conducted in a medical intensive care unit in a teaching hospital. Measurements were made at baseline and repeated after 1 and 6 hours of two randomized periods of 6 hours of PP with one of two support types: conventional foam mattress or air-cushioned mattress. RESULTS: After logarithmic transformation of the data, an analysis of variance (ANOVA) showed that IAP and PDR(ICG )were significantly influenced by the type of support during PP with an increase in IAP (P < 0.05 by ANOVA) and a decrease in PDR(ICG )on the foam mattress (P < 0.05 by ANOVA). Conversely, the measurements of EVLW did not show significant modification between the two supports whatever the posture. The ratio of the arterial oxygen tension to the fraction of inspired oxygen significantly increased in PP (P < 0.0001 by ANOVA) without any influence of the support. CONCLUSION: In comparison with a conventional foam mattress, the use of an air-cushioned mattress limited the increase in IAP and prevented the decrease in PDR(ICG )related to PP in patients with ARDS. Conversely, the type of support did not influence EVLW or oxygenation

Generation of a single pulmonary pressure-volume curve does not durably affect oxygenation in patients with acute respiratory distress syndrome

INTRODUCTION: It is possible that taking a static pressure-volume (PV) measurement could durably affect oxygenation and thus interfere with early evaluation of a therapeutic intervention delivered just after that measurement. The aim of the present study was to investigate the effects over time of a single static PV measurement on gas exchange and haemodynamics; the PV measurements were taken using a super syringe and by using the constant flow method in patients with acute respiratory distress syndrome. METHOD: We conducted a prospective, randomized and controlled interventional study in an intensive care unit. The study was conducted in 17 patients with early acute respiratory distress syndrome ventilated with a tidal volume of 6.9 ± 1.0 ml/kg, a plateau pressure of 27 ± 7 cmH(2)O and a positive end-expiratory pressure [PEEP] of 10 cmH(2)O. They were all evaluated for 1 hour after each of the following two measurements was taken and during a control period (in a randomized order): generation of a PV curve using a 2 l super syringe (PV(SS); insufflated volume = 1824 ± 381 ml, plateau pressure = 46 ± 9 cmH(2)O); and generation of a PV curve using the constant flow method on the ventilator (PV(CF); insufflated volume = 1120 ± 115 ml in zero end-expiratory pressure after 20 s expiratory pause, plateau pressure = 46 ± 11 cmH(2)O). The maximal airway pressure allowed during PV measurement was 60 cmH(2)O. PEEP was set to 10 cmH(2)O immediately after PV measurement. Partial arterial oxygen tension (Pao(2)), partial carbon dioxide tension (Paco(2)) and mean arterial pressure were recorded each minute. RESULTS: PV measurement did not significantly affect Pao(2), Paco(2), mean arterial pressure and lung mechanics. Two patients exhibited a sustained increase in Pao(2 )by more than 20% after PV(CF )(>60 minutes). Two patients exhibited a decrease in Pao(2 )by more than 20% after PV(SS), which was sustained in one. These latter patients had an upper inflection point identified on the PV curve. After PV(SS), Paco(2 )increased by more than 10 mmHg in two patients and returned to baseline values after 15 minutes. One patient exhibited a decrease in mean arterial pressure by more than 10 mmHg for less than 5 minutes after PV(SS )and one patient after PV(CF). CONCLUSION: Evaluation of the effects of a strategy aimed at improving oxygenation can be reliably recorded early after a single PV measurement that is not followed by a change in PEEP level. PV measurement using the constant flow method improves oxygenation in a limited number of patients

High levels of circulating leukocyte microparticles are associated with better outcome in acute respiratory distress syndrome

International audienceINTRODUCTION: The current study has addressed the presence and the cellular origin of microparticles (MP) isolated from bronchoalveolar lavage (BAL) fluid and from blood samples from patients with acute respiratory distress syndrome (ARDS). Their prognostic interest was also investigated. METHODS: Fifty-two patients were included within the first 24 hours of ARDS. They were compared to spontaneous breathing (SB) and ventilated control (VC) groups. Bronchoalveolar lavage (BAL) and blood samples were obtained on Day 1 and Day 3 in an ARDS group. Leukocyte microparticles (LeuMP), neutrophil microparticles (NeuMP), endothelial microparticles (EMP), and platelet microparticles (PMP) were measured in arterial blood and in BAL samples by flow cytometry. Mortality from all causes was recorded at Day 28. RESULTS: All MP subpopulations were detected in BAL. However, only LeuMP and NeuMP were elevated in ARDS patients compared to the SB group (P = 0.002 for both). Among ARDS patients, higher levels of LeuMP were detected in blood (Day 1) and in BAL (Day 3) in survivors as compared with the non survivors. Circulating LeuMP >60 elements/microliter detectable on Day 1 of ARDS, was associated with a higher survival rate (odds ratio, 5.26; 95% confidence interval, 1.10 to 24.99; P = 0.037). CONCLUSIONS: The identification of the cellular origin of microparticles at the onset of ARDS has identified LeuMP as a biomarker of prognostic significance. The higher levels of LeuMP in survivors could be associated with a protective role of this MP subpopulation. This hypothesis needs further investigations

Early-onset ventilator-associated pneumonia in adults randomized clinical trial: comparison of 8 versus 15 days of antibiotic treatment

International audiencePurposeThe optimal treatment duration for ventilator-associated pneumonia is based on one study dealing with late-onset of the condition. Shortening the length of antibiotic treatment remains a major prevention factor for the emergence of multiresistant bacteria.ObjectiveTo demonstrate that 2 different antibiotic treatment durations (8 versus 15 days) are equivalent in terms of clinical cure for early-onset ventilator-associated pneumonia.MethodsRandomized, prospective, open, multicenter trial carried out from 1998 to 2002.MeasurementsThe primary endpoint was the clinical cure rate at day 21. The mortality rate was evaluated on days 21 and 90.Results225 patients were included in 13 centers. 191 (84.9%) patients were cured: 92 out of 109 (84.4%) in the 15 day cohort and 99 out of 116 (85.3%) in the 8 day cohort (difference = 0.9%, odds ratio = 0.929). 95% two-sided confidence intervals for difference and odds ratio were [−8.4% to 10.3%] and [0.448 to 1.928] respectively. Taking into account the limits of equivalence (10% for difference and 2.25 for odds ratio), the objective of demonstrative equivalence between the 2 treatment durations was fulfilled. Although the rate of secondary infection was greater in the 8 day than the 15 day cohort, the number of days of antibiotic treatment remained lower in the 8 day cohort. There was no difference in mortality rate between the 2 groups on days 21 and 90.ConclusionOur results suggest that an 8-day course of antibiotic therapy is safe for early-onset ventilator-associated pneumonia in intubated patients

Ameba-associated Microorganisms and Diagnosis of Nosocomial Pneumonia

Ameba-associated microorganisms should be suspected when conventional microbiologic test results are negative