Blood fibrocytes are recruited during acute exacerbations of chronic obstructive pulmonary disease through a CXCR4-dependent pathway.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by peribronchial fibrosis. The chronic course of COPD is worsened by recurrent acute exacerbations. OBJECTIVE: The aim of the study was to evaluate the recruitment of blood fibrocytes in patients with COPD during exacerbations and, subsequently, to identify potential mechanisms implicated in such recruitment. METHODS: Using flow cytometry, we quantified circulating fibrocytes and characterized their chemokine receptor expression in 54 patients with COPD examined during an acute exacerbation (V1) and 2 months afterward (V2) and in 40 control subjects. The role of the chemokines CXCL12 and CCL11 in fibrocyte migration was investigated by using a chemotaxis assay. Patients were followed for up to 3 years after V1. RESULTS: We demonstrated a significantly increased number of circulating fibrocytes at V1 compared with control subjects. The number of circulating fibrocytes decreased at V2. A high percentage of circulating fibrocytes during exacerbation was associated with increased risk of death. The percentage of fibrocytes at V2 was negatively correlated with FEV1, forced vital capacity, FEV1/forced vital capacity ratio, transfer lung capacity of carbon monoxide, and Pao2. Fibrocytes highly expressed CXCR4 and CCR3, the chemokine receptors for CXCL12 and CCL11, respectively. Fibrocytes collected from patients with COPD at V1 had increased chemotactic migration in response to CXCL12 but not to CCL11 compared with those from control subjects. Plerixafor, a CXCR4 antagonist, decreased fibrocyte migration to plasma from patients with exacerbating COPD. CONCLUSION: Blood fibrocytes are recruited during COPD exacerbations and related to mortality and low lung function. The CXCL12/CXCR4 axis is involved in such fibrocyte recruitment (Firebrob study; ClinicalTrials NCT01196832).

Impacts of three inspiratory muscle training programs on inspiratory muscles strength and endurance among intubated and mechanically ventilated patients with difficult weaning: a multicentre randomised controlled trial.

BACKGROUND: Inspiratory muscle training (IMT) is well-established as a safe option for combating inspiratory muscles weakness in the intensive care setting. It could improve inspiratory muscle strength and decrease weaning duration but a lack of knowledge on the optimal training regimen raise to inconsistent results. We made the hypothesis that an innovative mixed intensity program for both endurance and strength improvement could be more effective. We conducted a multicentre randomised controlled parallel trial comparing the impacts of three IMT protocols (low, high, and mixed intensity) on inspiratory muscle strength and endurance among difficult-to-wean patients. METHODS: Ninety-two patients were randomly assigned to three groups with different training programs, where each performed an IMT program twice daily, 7 days per week, from inclusion until successful extubation or 30 days. The primary outcome was maximal inspiratory pressure (MIP) increase. Secondary outcomes included peak pressure (Ppk) increase as an endurance marker, mechanical ventilation (MV) duration, ICU length of stay, weaning success defined by a 2-day ventilator-free after extubation, reintubation rate and safety. RESULTS: MIP increases were 10.8 ± 11.9 cmH2O, 4.5 ± 14.8 cmH2O, and 6.7 ± 14.5 cmH2O for the mixed intensity (MI), low intensity (LI), and high intensity (HI) groups, respectively. There was a non-statistically difference between the MI and LI groups (mean adjusted difference: 6.59, 97.5% CI [- 14.36; 1.18], p = 0.056); there was no difference between the MI and HI groups (mean adjusted difference: - 3.52, 97.5% CI [- 11.57; 4.53], p = 0.321). No significant differences in Ppk increase were observed among the three groups. Weaning success rate observed in MI, HI and LI group were 83.7% [95% CI 69.3; 93.2], 82.6% [95% CI 61.2; 95.0] and 73.9% [95% CI 51.6; 89.8], respectively. MV duration, ICU length of stay and reintubation rate had similar values. Over 629 IMT sessions, six adverse events including four spontaneously reversible bradycardia in LI group were possibly related to the study. CONCLUSIONS: Among difficult-to-wean patients receiving invasive MV, no statistically difference was observed in strength and endurance progression across three different IMT programs. IMT appears to be feasible in usual cares, but some serious adverse events such as bradycardia could motivate further research on the specific impact on cardiac system. Trial registration Clinicaltrials.gov identifier: NCT02855619. Registered 28 September 2014.

Effects of mechanical in-exsufflation in preventing postextubation acute respiratory failure in intensive care acquired weakness patients: a randomized controlled trial.

OBJECTIVE: We hypothesized that the use of mechanical insufflation-exsufflation can reduce the incidence of acute respiratory failure within the 48-hour post-extubation period in intensive care unit-acquired weakness patients. METHODS: This was a prospective randomized controlled open-label trial. Patients diagnosed with intensive care unit-acquired weakness were consecutively enrolled based on a Medical Research Council score ≤ 48/60. The patients randomly received two daily sessions; in the control group, conventional chest physiotherapy was performed, while in the intervention group, chest physiotherapy was associated with mechanical insufflation-exsufflation. The incidence of acute respiratory failure within 48 hours of extubation was evaluated. Similarly, the reintubation rate, intensive care unit length of stay, mortality at 28 days, and survival probability at 90 days were assessed. The study was stopped after futility results in the interim analysis. RESULTS: We included 122 consecutive patients (n = 61 per group). There was no significant difference in the incidence of acute respiratory failure between treatments (11.5% control group versus 16.4%, intervention group; p = 0.60), the need for reintubation (3.6% versus 10.7%; p = 0.27), mean length of stay (3 versus 4 days; p = 0.33), mortality at Day 28 (9.8% versus 15.0%; p = 0.42), or survival probability at Day 90 (21.3% versus 28.3%; p = 0.41). CONCLUSION: Mechanical insufflation-exsufflation combined with chest physiotherapy seems to have no impact in preventing postextubation acute respiratory failure in intensive care unit-acquired weakness patients. Similarly, mortality and survival probability were similar in both groups. Nevertheless, given the early termination of the trial, further clinical investigation is strongly recommended. CLINICAL TRIALS REGISTER: NCT01931228.

Severe community-acquired Enterobacter pneumonia: a plea for greater awareness of the concept of health-care-associated pneumonia.

BACKGROUND: Patients with Enterobacter community-acquired pneumonia (EnCAP) were admitted to our intensive care unit (ICU). Our primary aim was to describe them as few data are available on EnCAP. A comparison with CAP due to common and typical bacteria was performed. METHODS: Baseline clinical, biological and radiographic characteristics, criteria for health-care-associated pneumonia (HCAP) were compared between each case of EnCAP and thirty age-matched typical CAP cases. A univariate and multivariate logistic regression analysis was performed to determine factors independently associated with ENCAP. Their outcome was also compared. RESULTS: In comparison with CAP due to common bacteria, a lower leukocytosis and constant HCAP criteria were associated with EnCAP. Empiric antibiotic therapy was less effective in EnCAP (20%) than in typical CAP (97%) (p < 0.01). A delay in the initiation of appropriate antibiotic therapy (3.3 ± 1.6 vs. 1.2 ± 0.6 days; p < 0.01) and an increase in duration of mechanical ventilation (8.4 ± 5.2 vs. 4.0 ± 4.3 days; p = 0.01) and ICU stay were observed in EnCAP patients. CONCLUSIONS: EnCAP is a severe infection which is more consistent with HCAP than with typical CAP. This retrospectively suggests that the application of HCAP guidelines should have improved EnCAP management.

Pseudomonas aeruginosa acquisition on an intensive care unit: relationship between antibiotic selective pressure and patients' environment.

INTRODUCTION: The purpose of this study was to investigate the relationship among Pseudomonas aeruginosa acquisition on the intensive care unit (ICU), environmental contamination and antibiotic selective pressure against P. aeruginosa. METHODS: An open, prospective cohort study was carried out in a 16-bed medical ICU where P. aeruginosa was endemic. Over a six-month period, all patients without P. aeruginosa on admission and with a length of stay >72 h were included. Throat, nasal, rectal, sputum and urine samples were taken on admission and at weekly intervals and screened for P. aeruginosa. All antibiotic treatments were recorded daily. Environmental analysis included weekly tap water specimen culture and the presence of other patients colonized with P. aeruginosa. RESULTS: A total of 126 patients were included, comprising 1,345 patient-days. Antibiotics were given to 106 patients (antibiotic selective pressure for P. aeruginosa in 39). P. aeruginosa was acquired by 20 patients (16%) and was isolated from 164/536 environmental samples (31%). Two conditions were independently associated with P. aeruginosa acquisition by multivariate analysis: (i) patients receiving ≥3 days of antibiotic selective pressure together with at least one colonized patient on the same ward on the previous day (odds ratio (OR) = 10.3 ((% confidence interval (CI): 1.8 to 57.4); P = 0.01); and (ii) presence of an invasive device (OR = 7.7 (95% CI: 2.3 to 25.7); P = 0.001). CONCLUSIONS: Specific interaction between both patient colonization pressure and selective antibiotic pressure is the most relevant factor for P. aeruginosa acquisition on an ICU. This suggests that combined efforts are needed against both factors to decrease colonization with P. aeruginosa.

Characterization of acute kidney injury in critically ill patients with severe coronavirus disease 2019.

BACKGROUND: Coronavirus disease 2019 (COVID-19)-associated acute kidney injury (AKI) frequency, severity and characterization in critically ill patients has not been reported. METHODS: Single-centre cohort performed from 3 March 2020 to 14 April 2020 in four intensive care units in Bordeaux University Hospital, France. All patients with COVID-19 and pulmonary severity criteria were included. AKI was defined using Kidney Disease: Improving Global Outcomes (KDIGO) criteria. A systematic urinary analysis was performed. The incidence, severity, clinical presentation, biological characterization (transient versus persistent AKI; proteinuria, haematuria and glycosuria) and short-term outcomes were evaluated. RESULTS: Seventy-one patients were included, with basal serum creatinine (SCr) of 69 ± 21 µmol/L. At admission, AKI was present in 8/71 (11%) patients. Median [interquartile range (IQR)] follow-up was 17 (12-23) days. AKI developed in a total of 57/71 (80%) patients, with 35% Stage 1, 35% Stage 2 and 30% Stage 3 AKI; 10/57 (18%) required renal replacement therapy (RRT). Transient AKI was present in only 4/55 (7%) patients and persistent AKI was observed in 51/55 (93%). Patients with persistent AKI developed a median (IQR) urine protein/creatinine of 82 (54-140) (mg/mmol) with an albuminuria/proteinuria ratio of 0.23 ± 20, indicating predominant tubulointerstitial injury. Only two (4%) patients had glycosuria. At Day 7 after onset of AKI, six (11%) patients remained dependent on RRT, nine (16%) had SCr >200 µmol/L and four (7%) had died. Day 7 and Day 14 renal recovery occurred in 28% and 52%, respectively. CONCLUSION: Severe COVID-19-associated AKI is frequent, persistent, severe and characterized by an almost exclusive tubulointerstitial injury without glycosuria.

Helmet with specific settings versus facemask for noninvasive ventilation.

OBJECTIVE: To compare the physiologic effects of noninvasive pressure-support ventilation (NPSV) delivered by a facemask, a helmet with the same settings, and a helmet with specific settings. Inspiratory muscle effort, gas exchange, patient-ventilator synchrony, and comfort were evaluated. DESIGN: Prospective crossover study. SETTING: A 13-bed medical intensive care unit in a university hospital. PATIENTS: Eleven patients at risk for respiratory distress requiring early NPSV after extubation. INTERVENTION: One hour after extubation, three 20-minute NPSV periods were delivered in a random order by facemask, helmet, and helmet with 50% increases in both pressure support and positive end-expiratory pressure and with the highest pressurization rate (95% max). MEASUREMENTS AND MAIN RESULTS: Flow and airway, esophageal, and gastric pressure signals were measured under the three NPSV conditions and during spontaneous breathing. Compared with the facemask, the helmet with the same settings resulted in a greater inspiratory muscle effort, but this difference was abolished by the specific settings (pressure-time product in cm H2O.s.min, 63.8 [27.3-85.9], 81.8 [36.0-111.5], and 58.0 [25.4-79.5], respectively, p < 0.05, compared with 209.3 [29.8-239.6] during spontaneous breathing). Compared with the facemask, the helmet with the same settings worsened patient-ventilator synchrony, as indicated by longer triggering-on and cycling-off delays (0.14 [0.11-0.20] seconds vs. 0.32 [0.26-0.43] seconds, p < 0.05; and 0.20 [0.08-0.24] seconds vs. 0.27 [0.25-0.35] seconds, p < 0.01, respectively). The specific settings significantly improved the triggering-on delay compared with the helmet without specific settings (p < 0.01). Tolerance was the same with the three methods. CONCLUSIONS: Our results suggest that increasing both the pressure-support level and positive end-expiratory pressure and using the highest pressurization rate may be advisable when providing NPSV via a helmet.

The sustainable impact of an educational approach to improve the appropriateness of laboratory test orders in the ICU.

INTRODUCTION: Few studies described strategies to improve the use of diagnostic tests in intensive care units (ICU). No study assessed whether their impact was sustained or not. In this study, we assessed whether a multi-faceted intervention for more appropriate use of laboratory testing can decrease the number of tests, is sustainable, is not associated with additional morbidity and represents a potential cost saving. MATERIAL AND METHODS: An open-label prospective cohort study in two separated units of the same medical intensive care unit (ICU) including respectively 3315 and 2392 consecutive patients. After the observation period (2010), a reduction in ICU A of unnecessary diagnostics tests as part of a program including senior supervisory of juniors' orders, encouragements for orders containment at each everyday round discussions (period 2; 2011). Period 3 (2012) consisted in the prolongation of the protocol as a routine care without supervision; Period 4 (2013) was a new period of observation without intervention. No modification was implemented in ICU B in periods 2-4. RESULTS: After the intervention, a decrease in the overall number of tests per ICU-patient-days (37.3±5.5 (baseline) to 15.2±3.2 (- 59%); p<0.0001) was observed. The total cost of the tests decreased from 239±41 to 104±28 euros per ICU-patient days; p<0.0001. The effect on laboratory test orders was sustainable in period 3 (-49%) and 4 (-30%). No significant secondary effect of the intervention was observed in period 2. In ICU B, there was no significant change in the overall laboratory test orders in between the periods. CONCLUSIONS: Laboratory test containment is effective, likely safe and sustainable provided that an educational program is repeatedly promoted, that it makes sense for the whole team, that senior and junior physicians are both committed in the program, and that encouragements for laboratory orders containment at each everyday round discussions.

Tailoring Empirical Antimicrobial Therapy in Subjects With Ventilator-Associated Pneumonia With a 10-Hour E-Test Approach.

BACKGROUND: In a previous study of subjects suspected of having ventilator-associated pneumonia, a rapid susceptibility testing approach by using ETEST (BioMérieux) strips directly applied to bronchoalveolar lavage samples provided valuable information at hour 24. The primary objective of this study was to assess a new direct specimen testing by using an even more-rapid E-test approach (at hour 10), which could promote an early de-escalation of the antimicrobial therapy. METHODS: Twenty-eight subjects with ventilator-associated pneumonia admitted to a medical ICU were prospectively included. In parallel with standard routine methods, E-test strips were directly applied onto agar plates seeded with bronchoalveolar lavage samples and were analyzed after 10 h of incubation. E-test results were used to identify potential drug choices by simulating clinical decision making if the microscopy results had been available at the point of care. These choices were analyzed for concordance with the narrowest adequate antimicrobial therapy according to the Minimum Inhibitory Concentrations (MICs) provided by the reference method (ie, the laboratory routine diagnostic). RESULTS: At hour 10, direct specimen testing was readable in 18 of 28 bronchoalveolar lavage samples (64%). Total agreement between the 10-h direct specimen testing approach and the laboratory routine diagnostic approach was 90%, with a sensitivity of 83% and a specificity of 95%, with 8% major errors and 3% very major errors. The concordance between the 2 tests was very good (kappa = 0.79). If the 10-h E-test results were taken into account, then an early de-escalation strategy would have been possible in 10 of 18 cases (55%) at hour 10. CONCLUSIONS: This rapid susceptibility testing approach provided early (10 h) and valuable information that could lead to an early adjustment of empirical antimicrobial treatment in a ventilator-associated pneumonia setting. (ClinicalTrials.gov registration NCT01266863.).

Intrapulmonary percussive ventilation superimposed on conventional ventilation: bench study of humidity and ventilator behaviour.

OBJECTIVE: Intrapulmonary percussive ventilation (IPV) is a form of high-frequency ventilation that can be superimposed on spontaneous breathing or conventional ventilation. Drawbacks include difficulties achieving adequate airway humidification and an inability to monitor delivered volumes and pressures, which may vary with patient characteristics. The objectives of this study were to assess various humidification set-ups, to measure intrapulmonary pressures and volumes resulting from IPV superimposed on a conventional driving ventilator (DV) and to test several ventilators regarding their ability to accept added IPV. DESIGN: Bench study in a test-lung set-up was used to measure humidification and the effects of adding IPV to a DV under various conditions of compliance, resistance, plateau and positive end-expiratory pressures. Then, five ventilators were tested in combination with IPV. MEASUREMENTS AND RESULTS: Adequate humidification required a heated humidifier on the inspiratory line downstream of the IPV device. IPV increased end-inspiratory intrapulmonary pressures up to 10 cmH(2)O, increased delivered volumes up to 237 ml and generated intrinsic PEEP from 1.7 to 4.3 cmH(2)O when no PEEP was set on the DV. Intrinsic PEEP was lower or absent when PEEP was set on the DV. With most tested ventilators, IPV prevented reliable flow monitoring. Autotriggering and missing cycles were common and the PEEP effect varied across DVs. CONCLUSION: Achieving adequate humidification with IPV requires a specific set-up. Superimposing IPV on standard ventilation can increase intrapulmonary pressures and tidal volumes importantly and interfere with the triggering sensors of the ventilator. These factors must be taken into account before clinical use.

Hemodynamic Assessment of Patients With Septic Shock Using Transpulmonary Thermodilution and Critical Care Echocardiography: A Comparative Study.

BACKGROUND: To assess the agreement between transpulmonary thermodilution (TPT) and critical care echocardiography (CCE) in ventilated patients with septic shock. METHODS: Ventilated patients in sinus rhythm requiring advanced hemodynamic assessment for septic shock were included in this prospective multicenter descriptive study. Patients were assessed successively using TPT and CCE in random order. Data were interpreted independently at bedside by two investigators who proposed therapeutic changes on the basis of predefined algorithms. TPT and CCE hemodynamic assessments were reviewed offline by two independent experts who identified potential sources of discrepant results by consensus. Lactate clearance and outcome were studied. RESULTS: A total of 137 patients were studied (71 men; age, 61 ± 15 years; Simplified Acute Physiologic Score, 58 ± 18; Sequential Organ Failure Assessment, 10 ± 3). TPT and CCE interpretations at bedside were concordant in 87/132 patients (66%) without acute cor pulmonale (ACP), resulting in a moderate agreement (kappa, 0.48; 95% CI, 0.37-0.60). Experts' adjudications were concordant in 100/129 patients without ACP (77.5%), resulting in a good intertechnique agreement (kappa, 0.66; 95% CI, 0.55-0.77). In addition to ACP (n = 8), CCE depicted a potential source of TPT inaccuracy in 8/29 patients (28%). Lactate clearance at H6 was similar irrespective of the concordance of online interpretations of TPT and CCE (55/84 [65%] vs 32/45 [71%], P = .55). ICU and day 28 mortality rates were similar between patients with concordant and discordant interpretations (29/87 [36%] vs 13/45 [29%], P = .60; and 31/87 [36%] vs 16/45 [36%], P = .99, respectively). CONCLUSIONS: Agreement between TPT and CCE was moderate when interpreted at bedside and good when adjudicated offline by experts, but without impact on lactate clearance and mortality.

Effects of mechanical in-exsufflation in preventing postextubation acute respiratory failure in intensive care acquired weakness patients: a randomized controlled trial / Efeitos da insuflação-exsuflação mecânica na prevenção da insuficiência respiratória aguda pós-extubação em pacientes com fraqueza adquirida em terapia intensiva: um estudo controlado e randomizado

ABSTRACT Objective: We hypothesized that the use of mechanical insufflation-exsufflation can reduce the incidence of acute respiratory failure within the 48-hour post-extubation period in intensive care unit-acquired weakness patients. Methods: This was a prospective randomized controlled open-label trial. Patients diagnosed with intensive care unit-acquired weakness were consecutively enrolled based on a Medical Research Council score ≤ 48/60. The patients randomly received two daily sessions; in the control group, conventional chest physiotherapy was performed, while in the intervention group, chest physiotherapy was associated with mechanical insufflation-exsufflation. The incidence of acute respiratory failure within 48 hours of extubation was evaluated. Similarly, the reintubation rate, intensive care unit length of stay, mortality at 28 days, and survival probability at 90 days were assessed. The study was stopped after futility results in the interim analysis. Results: We included 122 consecutive patients (n = 61 per group). There was no significant difference in the incidence of acute respiratory failure between treatments (11.5% control group versus 16.4%, intervention group; p = 0.60), the need for reintubation (3.6% versus 10.7%; p = 0.27), mean length of stay (3 versus 4 days; p = 0.33), mortality at Day 28 (9.8% versus 15.0%; p = 0.42), or survival probability at Day 90 (21.3% versus 28.3%; p = 0.41). Conclusion: Mechanical insufflation-exsufflation combined with chest physiotherapy seems to have no impact in preventing postextubation acute respiratory failure in intensive care unit-acquired weakness patients. Similarly, mortality and survival probability were similar in both groups. Nevertheless, given the early termination of the trial, further clinical investigation is strongly recommended. Clinical Trials Register: NCT 01931228

RESUMO Objetivo: Verificar se o uso de insuflação-exsuflação mecânica pode reduzir a incidência da insuficiência respiratória aguda no período de 48 horas pós-extubação em pacientes com fraqueza adquirida em unidades de terapia intensiva. Métodos: Estudo prospectivo, randomizado, controlado e aberto. Os pacientes diagnosticados com fraqueza adquirida em unidade de terapia intensiva foram incluídos consecutivamente, com base em uma pontuação do Medical Research Council ≤ 48/60. Os pacientes receberam aleatoriamente duas sessões diárias; no grupo controle, realizou-se fisioterapia torácica convencional, enquanto no grupo intervenção, combinou-se fisioterapia torácica com insuflação-exsuflação mecânica. Avaliou-se a incidência de insuficiência respiratória aguda dentro de 48 horas após a extubação. Da mesma forma, avaliaram-se a taxa de reintubação, o tempo de permanência na unidade de terapia intensiva, a mortalidade aos 28 dias e a probabilidade de sobrevida aos 90 dias. O estudo foi interrompido após resultados de futilidade na análise intermediária. Resultados: Incluímos 122 pacientes consecutivos (n = 61 por grupo). Não houve diferença significativa na incidência de insuficiência respiratória aguda entre os tratamentos (11,5% no grupo controle versus 16,4% no grupo intervenção; p = 0,60), na necessidade de reintubação (3,6% versus 10,7%; p = 0,27), no tempo médio de internação (3 versus 4 dias; p = 0,33), na mortalidade aos 28 dias (9,8% versus 15,0%; p = 0,42) ou na probabilidade de sobrevida aos 90 dias (21,3% versus 28,3%; p = 0,41). Conclusão: A insuflação-exsuflação mecânica associada à fisioterapia torácica parece não ter impacto na prevenção da insuficiência respiratória aguda pós-extubação em pacientes com fraqueza adquirida na unidade de terapia intensiva. Da mesma forma, a mortalidade e a probabilidade de sobrevida foram semelhantes em ambos os grupos. No entanto, devido ao término precoce do estudo, recomenda-se enfaticamente uma investigação clínica mais aprofundada. Registro Clinical Trials: NCT 01931228

Multicentric Standardized Flow Cytometry Routine Assessment of Patients With Sepsis to Predict Clinical Worsening.

BACKGROUND: In this study, we primarily sought to assess the ability of flow cytometry to predict early clinical deterioration and overall survival in patients with sepsis admitted in the ED and ICU. METHODS: Patients admitted for community-acquired acute sepsis from 11 hospital centers were eligible. Early (day 7) and late (day 28) deaths were notified. Levels of CD64pos granulocytes, CD16pos monocytes, CD16dim immature granulocytes (IGs), and T and B lymphocytes were assessed by flow cytometry using an identical, cross-validated, robust, and simple consensus standardized protocol in each center. RESULTS: Among 1,062 patients screened, 781 patients with confirmed sepsis were studied (age, 67 ± 48 years; Simplified Acute Physiology Score II, 36 ± 17; Sequential Organ Failure Assessment, 5 ± 4). Patients were divided into three groups (sepsis, severe sepsis, and septic shock) on day 0 and on day 2. On day 0, patients with sepsis exhibited increased levels of CD64pos granulocytes, CD16pos monocytes, and IGs with T-cell lymphopenia. Clinical severity was associated with higher percentages of IGs and deeper T-cell lymphopenia. IG percentages tended to be higher in patients whose clinical status worsened on day 2 (35.1 ± 35.6 vs 43.5 ± 35.2, P = .07). Increased IG percentages were also related to occurrence of new organ failures on day 2. Increased IG percentages, especially when associated with T-cell lymphopenia, were independently associated with early (P < .01) and late (P < .01) death. CONCLUSIONS: Increased circulating IGs at the acute phase of sepsis are linked to clinical worsening, especially when associated with T-cell lymphopenia. Early flow cytometry could help clinicians to target patients at high risk of clinical deterioration. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01995448; URL: www.clinicaltrials.gov.

A postural change test improves the prediction of a radiological maxillary sinusitis by ultrasonography in mechanically ventilated patients.

OBJECTIVE: The aim of this study was to evaluate a postural change test during sinus ultrasound, compared with CT scan, in case of partial sinusogram to differentiate air-fluid level from mucosal thickening. DESIGN: Prospective clinical investigation. SETTING: Medical intensive care unit. PATIENTS: 150 intubated patients. INTERVENTIONS: Patients were examined by sinus ultrasound in half-sitting position. A partial sinusogram was defined as the sole visualization of the hyperechogenic posterior wall of the sinus. In this situation, a postural change was performed and ultrasound was achieved in supine position. If the partial sinusogram disappeared when the patient was placed in a supine position (positive test), the partial sinusogram was an air-fluid level. If the partial sinusogram did not disappear (negative test), we considered it as a mucosal thickening. The CT and ultrasound were performed on the same day. Radiological maxillary sinusitis (RMS) on CT was defined as the presence of an air-fluid level. Absence of RMS on CT was defined as normal sinus or as the presence of mucosal thickening. MEASUREMENTS AND RESULTS: 300 sinuses were examined. A partial sinusogram was found in 90 sinuses and CT scan confirmed the presence of RMS in 55 sinuses (61%). Sensitivity, specificity, positive predictive value, and negative predictive value of postural change test compared with CT were, respectively, 94.6, 85.6, 91.2 and 90.9%. The positive predictive value increased from 61 to 91.2% after the postural change test. CONCLUSIONS: In case of a partial sinusogram, a postural change increases the accuracy of ultrasound to diagnose RMS.

Ultrasonographic diaphragmatic excursion is inaccurate and not better than the MRC score for predicting weaning-failure in mechanically ventilated patients.

PURPOSE: To assess the ability of diaphragmatic ultrasound (US) to predict weaning failure in mechanically ventilated patients undergoing a first spontaneous breathing trial (SBT). METHODS: During a 4-month period, 67 consecutive patients eligible for a first SBT underwent US measurements of maximal diaphragmatic excursion (MDE) by a right anterior subcostal approach. Weaning failure was defined as either the failure of SBT or the need for resumption of ventilatory support for acute respiratory failure or death within 48h following successful extubation. The accuracy of diaphragmatic ultrasound and the Medical Research Council (MRC) score when predicting weaning failure was assessed via a receiver operating curve analysis. RESULTS: The feasibility rate for the ultrasound measurements was 63%. Mean values of MDE were significantly higher in patients who succeeded at their first weaning attempt (4.1±2.1 versus 3±1.8cm, P=0.04). Using a threshold of MDE≤2.7cm, the sensitivity and specificity of diaphragmatic ultrasound in predicting weaning failure were 59% [39-77%] and 71% [57-82%] with an AUC at 0.65 [0.51-0.78]. There was no significant difference between MDE values and MRC scores for predicting weaning failure (P=0.73). CONCLUSION: A decrease in MDE values may be associated with an unfavourable weaning outcome. Diaphragmatic excursion measured by ultrasound is however unable by itself to predict weaning failure at the bedside of patients undergoing a first spontaneous breathing trial and does not provide any additional value compared to the MRC score.

Intermittent noninvasive ventilation after extubation in patients with chronic respiratory disorders: a multicenter randomized controlled trial (VHYPER).

PURPOSE: Early noninvasive ventilation (NIV) after extubation decreases the risk of respiratory failure and lowers 90-day mortality in patients with hypercapnia. Patients with chronic respiratory disease are at risk of extubation failure. Therefore, it could be useful to determine the role of NIV with a discontinuous approach, not limited to patients with hypercapnia. We assessed the efficacy of early NIV in decreasing respiratory failure after extubation in patients with chronic respiratory disorders. METHODS: A prospective randomized controlled multicenter study was conducted. We enrolled 144 mechanically ventilated patients with chronic respiratory disorders who tolerated a spontaneous breathing trial. Patients were randomly allocated after extubation to receive either NIV (NIV group, n = 72), performed with a discontinuous approach, for the first 48 h, or conventional oxygen treatment (usual care group, n = 72). The primary endpoint was decreased respiratory failure within 48 h after extubation. Analysis was by intention to treat. This trial was registered with ClinicalTrials.gov (NCT01047852). RESULTS: Respiratory failure after extubation was less frequent in the NIV group: 6 (8.5%) versus 20 (27.8%); p = 0.0016. Six patients (8.5%) in the NIV group versus 13 (18.1%) in the usual care group were reintubated; p = 0.09. Intensive care unit (ICU) mortality and 90-day mortality did not differ significantly between the two groups (p = 0.28 and p = 0.33, respectively). Median postrandomization ICU length of stay was lower in the usual care group: 3 days (IQR 2-6) versus 4 days (IQR 2-7; p = 0.008). Patients with hypercapnia during a spontaneous breathing trial were at risk of developing postextubation respiratory failure [adjusted odds ratio (95% CI) = 4.56 (1.59-14.00); p = 0.006] and being intubated [adjusted odds ratio (95% CI) = 3.60 (1.07-13.31); p = 0.04]. CONCLUSIONS: Early NIV performed following a sequential protocol for the first 48 h after extubation decreased the risk of respiratory failure in patients with chronic respiratory disorders. Reintubation and mortality did not differ between NIV and conventional oxygen therapy.

Transnasal puncture based on echographic sinusitis evidence in mechanically ventilated patients with suspicion of nosocomial maxillary sinusitis.

OBJECTIVE: The aim of this prospective study was to evaluate the value of sinus echography results to directly indicate a transnasal puncture in intubated patients with suspicion of nosocomial maxillary sinusitis. DESIGN: prospective clinical investigation. SETTING: medical intensive care unit. PATIENTS: sixty patients undergoing intubation and mechanical ventilation more than 2 days, with a clinical suspicion of maxillary sinusitis with purulent nasal discharge. INTERVENTIONS: 120 sinuses were examined by sinus ultrasound. The image defined as normal was an acoustic shadow arising from the front wall. Two levels of positive echography were described: (1) a partial sinusogram was defined as the visualization of the hyperechogenic posterior wall of the sinus; and (2) a complete sinusogram was defined as the hyperechogenic visualization of posterior wall and the extension by the internal and external walls of the sinus. When sinus ultrasound was positive, a transnasal puncture was performed the same day. The transnasal puncture was positive if a fluid was obtained from sinus aspiration. The transnasal puncture was negative if there was no aspirated material. MEASUREMENTS AND RESULTS: sinus ultrasound was positive in 84 cases (54 complete sinusograms and 30 partial sinusograms). Seventy-eight of 84 transnasal punctures were positive. Sensitivity of a sinusogram for obtaining positive transnasal puncture was 100%, and specificity was 86% (100% in case of complete sinusogram) in a clinically selected population. The only six negative transnasal punctures were performed in patients with partial sinusogram. CONCLUSIONS: Ultrasound sinusitis evidence seems to be of value to indicate and perform a transnasal puncture directly, avoiding CT exam.

Intrapulmonary percussive ventilation in acute exacerbations of COPD patients with mild respiratory acidosis: a randomized controlled trial [ISRCTN17802078].

INTRODUCTION: We hypothesized that the use of intrapulmonary percussive ventilation (IPV), a technique designed to improve mucus clearance, could prove effective in avoiding further deterioration in patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) with mild respiratory acidosis. METHODS: The study was performed in a medical intensive care unit of a university hospital. Thirty-three patients with exacerbations of COPD with a respiratory frequency >or= 25/min, a PaCO2 > 45 Torr and 7.35