Propensity-based study of aminoglycoside nephrotoxicity in patients with severe sepsis or septic shock.

To assess the risk of acute kidney injury (AKI) attributable to aminoglycosides (AGs) in patients with severe sepsis or septic shock, we performed a retrospective cohort study in one medical intensive care unit (ICU) in France. Patients admitted for severe sepsis/septic shock between November 2008 and January 2010 were eligible. A propensity score for AG administration was built using day 1 demographic and clinical characteristics. Patients still on the ICU on day 3 were included. Patients with renal failure before day 3 or endocarditis were excluded. The time window for assessment of renal risk was day 3 to day 15, defined according to the RIFLE (risk, injury, failure, loss, and end-stage renal disease) classification. The AKI risk was assessed by means of a propensity-adjusted Cox proportional hazards regression analysis. Of 317 consecutive patients, 198 received AGs. The SAPS II (simplified acute physiology score II) score and nosocomial origin of infection favored the use of AGs, whereas a preexisting renal insufficiency and the neurological site of infection decreased the propensity for AG treatment. One hundred three patients with renal failure before day 3 were excluded. AGs were given once daily over 2.6 ± 1.1 days. AKI occurred in 16.3% of patients in a median time of 6 (interquartile range, 5 to 10) days. After adjustment to the clinical course and exposure to other nephrotoxic agents between day 1 and day 3, a propensity-adjusted Cox proportional hazards regression analysis showed no increased risk of AKI in patients receiving AGs (adjusted relative risk = 0.75 [0.32 to 1.76]). In conclusion, in critically septic patients presenting without early renal failure, aminoglycoside therapy for less than 3 days was not associated with an increased risk of AKI.

Ultraviolet-B radiation modifies the quantitative and qualitative profile of flavonoids and amino acids in grape berries.

Grapevine cv. Tempranillo fruit-bearing cuttings were exposed to supplemental ultraviolet-B (UV-B) radiation under controlled conditions, in order to study its effect on grape traits, ripening, amino acids and flavonoid profile. The plants were exposed to two doses of UV-B biologically effective (5.98 and 9.66kJm(-2)d(-1)), applied either from fruit set to ripeness or from the onset of veraison to ripeness. A 0kJm(-2)d(-1) treatment was included as a control. UV-B did not significantly modify grape berry size, but increased the relative mass of berry skin. Time to reach ripeness was not affected by UV-B, which may explain the lack of changes in technological maturity. The concentration of must extractable anthocyanins, colour density and skin flavonols were enhanced by UV-B, especially in plants exposed from fruit set. The quantitative and qualitative profile of grape skin flavonols were modified by UV-B radiation. Monosubstituted flavonols relative abundance increased proportionally to the accumulated UV-B doses. Furthermore, trisubstituted forms, which where predominant in non-exposed berries, were less abundant as UV-B exposure increased. Although total free amino acid content remained unaffected by the treatments, the increased levels of gamma-aminobutyric acid (GABA), as well as the decrease in threonine, isoleucine, methionine, serine and glycine, revealed a potential influence of UV-B on the GABA-mediated signalling and amino acid metabolism. UV-B had an overall positive impact on grape berry composition.

Tracheal amylase dosage as a marker for microaspiration: a pilot study.

BACKGROUND: Devices that limit microaspiration through the cuffs of endotracheal tubes could help prevent ventilator-associated pneumonia (VAP). The amount of tracheal microaspirations could be a relevant study endpoint. The aim of our study was to assess whether amylase measured in tracheal secretions constituted a relevant marker for microaspiration. METHODS: Twenty-six patients, intubated for at least 48 h and supplied with a subglottic secretion-suctioning device, constituted a group with a high risk of microaspiration. Twelve non-ventilated patients that required a bronchoscopy procedure constituted a group with a low risk of microaspiration (the control group). Tracheal (T) amylase was compared between the groups. In the intubated group, a series of oral (O), subglottic (Sg) and tracheal (T) suction samples were collected and T/O, T/Sg, Sg/O amylase ratios were determined. RESULTS: Amylase was measured in 277 (89 Sg, 96 B, 92 T) samples from the intubated group and in 12 T samples from the control group. Tracheal amylase was lower in the control group than the intubated group (191 [10-917] vs. 6661 [2774-19,358] IU/L, P<0.001). Amylase gradually increased from tracheal (6661 [2774-19,358] IU/L), to subglottic (130,750 [55,257-157,717] IU/L), to oral samples (307,606 [200,725-461,300] IU/L), resulting in a median 5.5% T/O ratio. In a subset of intubated patients, T amylase samples were assessed in two different laboratories, and gave reproducible results. CONCLUSION: Tracheal amylase was easy to collect, transport, and measure. The T/O amylase ratio is a first step towards quantifying oropharyngeal to tracheal microaspiration in mechanically-ventilated patients.

Sedation during non-invasive ventilation.

Non-invasive ventilation (NIV) is increasingly used in patients with acute respiratory failure, but few data exist regarding current sedation practices during NIV. Mask intolerance or claustrophobia, and delirium and agitation, may lead to NIV failure, requiring endotracheal intubation. Judicious use of sedation during NIV could be one of the valuable options for some of these patients at risk of intubation. Although different sedatives have been used in published studies, the objectives of sedation are similar: allowing mitigation of patient discomfort and obtaining the desired level of sedation. Whatever the sedative used, the goal is to achieve sedation to a point where the patients are awake and arousable and comfortable. Pilot studies suggest that continuous infusion of a single sedative agent may decrease patient discomfort, with no significant effects on respiratory drive, respiratory pattern, or hemodynamics. In addition, gas exchange improved under NIV with sedation. While the current limited data available suggests that sedation during NIV is safe and feasible, more widespread application should await the results of randomized clinical trials.

Echocardiographic evaluation and N-terminal pro-brain natriuretic peptide measurement of patients hospitalized for heart failure during weaning from mechanical ventilation.

BACKGROUND: Weaning patients with heart failure who have required mechanical ventilation remains challenging. We evaluated echocardiographic indexes and N-terminal pro-brain natriuretic peptide (NT-proBNP) as markers of acute cardiac dysfunction before and after spontaneous breathing trials (SBT) in such patients to assess their ability to predict subsequent successful extubation. METHODS: Forty-four patients who underwent their first SBT were prospectively included. Plasma levels of NT-proBNP and transthoracic echocardiography indices including cardiac index, E/A ratio and E/Ea ratio were recorded immediately before commencing and just before the end of SBT. RESULTS: Ten patients (22.7%) failed their SBT. No significant difference was observed concerning baseline echocardiographic data and NT-proBNP level between the patients who succeeded the SBT or those that failed. Cardiac index increased significantly at end-SBT in patients who passed (3.3 [3.06-3.77] vs. 3 [2.68-3.3] L/min/m(2), P<0.001), whereas it remained unchanged in those that failed. E/Ea ratio (16.8 [8.5-27.3] vs. 10.7 [6.7-20.5], P=0.006) and NT-proBNP level (8199 [3106-10949] vs. 4200 [1855-7125] pg/mL, P=0.004) increased significantly in those who failed the SBT, in contrast to the weaning success group where they remained unchanged. CONCLUSION: Neither NT-proBNP level nor the studied echocardiographic indices before SBT were able to predict SBT outcome in patients presenting with severe heart failure. Failure to increase the cardiac index and increases in both E/Ea ratio and NT-proBNP levels were seen at end-SBT in patients who failed the SBT, and may reflect failure of myocardial reserve to cope with the stress of SBT.

[Where to manage community acquired pneumonia? The assessment of severity]. / Où traiter une pneumopathie aiguë communautaire: évaluation de la sévérité?

The assessment of severity. Severity assessment is a key element in the management of community-acquired pneumonia. This assessment will determine the level of diagnostic workup and treatment, as well as the site of care. Several tools have been developed to help this assessment. The Pneumonia Severity Index (PSI) or the CURB-65 can accurately identify patients with a low risk of death who might be considered for outpatient care while those with a high risk of death would be hospitalized. Nevertheless, PSI and CURB-65 are less accurate for identifying patients requiring admission to an intensive care unit (ICU). Different scores, such the American Thoracic Society criteria or the SMART-COP score, were built to predict need for admission to ICU, vasopressors or mechanical ventilation. Each score has its own strengths and weaknesses and physicians must be aware of these limitations. Although, severity assessment tools are useful guides in the management of patients with community acquired pneumonia, clinical judgment must remain decisive.

[Changes in inspiratory capacity during acute respiratory failure in COPD patients]. / Evolution de la capacité inspiratoire au cours de la BPCO décompensée.

INTRODUCTION: Inspiratory Capacity (IC), which reflects dynamic pulmonary hyperinflation, correlates with outcome in moderate exacerbation of COPD. Whether this is also true in COPD with acute respiratory failure (ARF) has not been studied. METHODS: A prospective multicenter assessment of IC measurement feasibility, reliability, time-course and relationship to outcome in COPD with ARF was conducted. Dyspnea (visual analogue scale) and IC were repeatedly measured. Outcome was classified as not favourable (death or intubation or non invasive ventilation increased or patient referred to ICU from respiratory ward) or favourable (none of the above criteria). RESULTS: Fifty patients were included and 48 analysed. IC measurement was possible in all but one patient and its coefficient of variation was 9+/-8%. Between inclusion into the study and discharge, IC increased from 39.9+/-15.5 to 50.2+/-14.5% pred (p<0.001) and dyspnea declined from 48+/-23 to 33+/-22 mm (p<0.001). Inclusion IC was not different on average between patients with or without favourable outcome. CONCLUSION: In COPD patients with ARF, IC measurement at bedside was feasible and reproducible. IC was low at entry and increased over time from inclusion to discharge tending to correlate with patient outcome.

Microclimate influence on mineral and metabolic profiles of grape berries.

The grape berry microclimate is known to influence berry quality. The effects of the light exposure of grape berry clusters on the composition of berry tissues were studied on the "Merlot" variety grown in a vineyard in Bordeaux, France. The light exposure of the fruiting zone was modified using different intensities of leaf removal, cluster position relative to azimuth, and berry position in the cluster. Light exposures were identified and classified by in situ measurements of berry temperatures. Berries were sampled at maturity (>19 Brix) for determination of skin and/or pulp chemical and metabolic profiles based on (1) chemical and physicochemical measurement of minerals (N, P, K, Ca, Mg), (2) untargeted 1H NMR metabolic fingerprints, and HPLC targeted analyses of (3) amino acids and (4) phenolics. Each profile defined by partial least-square discriminant analysis allowed us to discriminate berries from different light exposure. Discriminant compounds between shaded and light-exposed berries were quercetin-3-glucoside, kaempferol-3-glucoside, myricetin-3-glucoside, and isorhamnetin-3-glucoside for the phenolics, histidine, valine, GABA, alanine, and arginine for the amino acids, and malate for the organic acids. Capacities of the different profiling techniques to discriminate berries were compared. Although the proportion of explained variance from the 1H NMR fingerprint was lower compared to that of chemical measurements, NMR spectroscopy allowed us to identify lit and shaded berries. Light exposure of berries increased the skin and pulp flavonols, histidine and valine contents, and reduced the organic acids, GABA, and alanine contents. All the targeted and nontargeted analytical data sets used made it possible to discriminate sun-exposed and shaded berries. The skin phenolics pattern was the most discriminating and allowed us to sort sun from shade berries. These metabolite classes can be used to qualify berries collected in an undetermined environment. The physiological significance of light and temperature effects on berry composition is discussed.

[Non-invasive ventilation in immunosuppressed patients]. / La ventilation non invasive chez le patient immunodéprimé

INTRODUCTION: In immunosuppressed patients with acute respiratory insufficiency (ARI) mechanical ventilation is associated with a high mortality. Therefore, in this situation, avoidance of intubation could be an important objective. However, experience of non-invasive ventilation (NIV) in the immunosuppressed remains limited. STATE OF ART: The first descriptive studies have shown that NIV could be an alternative to intubation, particularly in patients with malignant haematological disorders. In a prospective randomised controlled study Antonelli et al. showed that the use of NIV significantly improved the prognosis of patients with ARI following organ transplantation. We have carried out a prospective randomised controlled trial in 52 immunosuppressed patients to determine whether NIV improved the prognosis in patients admitted to intensive care with pulmonary infiltrates, fever and ARI. The use of NIV was associated with significant reductions in the intubation rate, serious complications and ICU and hospital mortality. PERSPECTIVES: Further studies are needed in order to better define the patients susceptible to benefit from NIV, and to establish variables predictive of the success or the failure of the method. CONCLUSIONS: NIV leads to an improvement in the prognosis of some immunosuppressed patients admitted to intensive care.

[Association of type 1 neurofibromatosis and primary hyperparathyroidism]. / Association neurofibromatose de type I et hyperparathyroïdie primitive.

INTRODUCTION: The combination of neurofibromatosis type I with hyperparathyroidism is classical but rare. OBSERVATION: Our report is on the original observation of a patient affected with Von Recklinghausen's disease complicated by chronic restrictive breathing deficiency. After an intense breathing decompensation and a spreading convulsive attack, hyperparathyroidism was diagnosed. DISCUSSION: The similarity of the bone lesions seen in type I neurofibromatosis and in hyperparathyroidism strongly suggests a genetic link between these two pathologies. Hence, hyperparathyroidism should be searched for in all patients affected with Von Recklinghausen's disease, since the adjustment of hypercalcemia can lead to partial reversibility of the bone abnormalities.

Comparison of B-mode ultrasound and computed tomography in the diagnosis of maxillary sinusitis in mechanically ventilated patients.

OBJECTIVE: To compare B-mode ultrasound with sinus computed tomograph (CT) scan in the diagnosis of sinusitis in intubated patients undergoing mechanical ventilation. DESIGN: Prospective, clinical investigation. SETTING: Medical intensive care unit of a university hospital. PATIENTS: Fifty patients undergoing intubation and mechanical ventilation more than 2 days, with a clinical suspicion of paranasal sinusitis with purulent nasal discharge. INTERVENTIONS: One hundred paranasal sinuses were examined. A paranasal CT scan and a B-mode ultrasound were performed the same day. Radiologic maxillary sinusitis (RMS) was defined as complete opacification of the sinus or as the presence of an air-fluid level. Absence of RMS was defined as normal sinus or as the presence of mucosal thickening. Important RMS was defined by total opacity or air-fluid level larger than half of the sinus area. Moderate RMS was defined by air-fluid level inferior than half of the sinus area. For ultrasonographic procedure, the image defined as normal was an acoustic shadow arising from the front wall. Two levels of positive echography were described: 1) a moderate lesion was defined as the visualization only of the hyperechogenic posterior wall of the sinus; 2) an important lesion was defined as the hyperechogenic visualization of posterior wall and the extension by the internal wall of the sinus outlining the hypoechogenic sinus cavity. MEASUREMENTS AND MAIN RESULTS: Sensibility, specificity, positive predictive value, and negative predictive value of B-mode ultrasound compared with CT were, respectively: 100% (95% confidence intervals [95% CI] = 94.9-100.0), 96.7% (95% CI = 82.8-99.9), 98.6% (95% CI = 92.4-99.9), and 100% (95% CI = 88.1-100). The concordance between a moderate B-mode ultrasound lesion and a moderate RMS on CT, and between an important B-mode ultrasound lesion and an important RMS on CT, assessed using kappa statistics was 93%. The concordance between B-mode ultrasound's results and CT's results assessed using weighted kappa statistics was 97%. CONCLUSION: B-mode ultrasound may be proposed first-line in a ventilated patient with suspicion of maxillary sinusitis.

Prognostic score of short-term survival in HIV-infected patients admitted to medical intensive care units.

A retrospective cohort was set up to identify prognostic factors associated with in-hospital survival in HIV-infected patients admitted to medical intensive care units (MICUs), from 1991 to 1994. Survival from MICU admission to hospital discharge (or in-hospital fatal issue) was estimated and a prognostic score at MICU admission was developed. One hundred and thirty patients were recruited of whom 20% were AIDS-free prior to admission. In-hospital mortality rate was 65%. Median survival was 20 days. The following variables were predictive of mortality: Simplified Acute Physioloy Score II (SAPS II): (hazard ratio [HR]=1.5 for 10 points higher, P<10(-3)), time between HIV diagnosis and admission >5 years (HR=2.7, P<10(-4)), hypoalbuminaemia (HR=1.2 per 5 g/l lower, P=0.03). The prognostic score developed was: SAPS II+25 (if time between HIV diagnosis and MICU admission >5 years) albuminaemia (g/l). A new prognostic score including SAPS II, prior HIV history and albuminaemia better reflected the in-hospital mortality than SAPS II alone. Our findings may still be useful to better evaluate the immediate prognosis of current HIV-infected patients admitted to MICU, particularly those naive to antiretroviral therapy or in treatment failure.

Bronchoscopy with bronchoalveolar lavage via the laryngeal mask airway in high-risk hypoxemic immunosuppressed patients.

OBJECTIVE: Fiberoptic bronchoscopy (FOB) and bronchoalveolar lavage (BAL) are major tools in the diagnosis of pulmonary complications in immunocompromised patients. Nevertheless, severe hypoxemia is an accepted contraindication to FOB in nonintubated patients. The purpose of this study was to evaluate the feasibility and safety of laryngeal mask airway (LMA)-supported FOB with BAL in immunosuppressed patients with suspected pneumonia and severe hypoxemia. DESIGN: Prospective, clinical investigation. SETTING: Medical intensive care unit of a university hospital. PATIENTS: Forty-six immunosuppressed patients admitted to our intensive care unit with suspected pneumonia and Pao2/Fio2 < or = 125. INTERVENTIONS: After the administration of 0.3 mg x kg(-1) of etomidate, the patients were ventilated manually while receiving 1.0 Fio2. After the administration of 2.5 mg x kg(-1) of propofol, followed by an infusion of 9.1 +/- 2.3 mg x kg(-1) x hr(-1) of propofol, the LMA (size 3 or 4) was placed and connected to a bag-valve unit to allow manual ventilation with 1.0 Fio2. The FOB was introduced through a T-adapter attached to the LMA, and BAL was carried out with 150 mL of sterile 0.9% saline solution by sequential instillation and aspiration of 50-mL aliquots. MEASUREMENTS AND MAIN RESULTS: Three patients developed transient laryngospasm during passage of the bronchoscope via the LMA, which resolved with deepening of anesthesia. Changes in mean blood pressure, heart rate, Pao2/Fio2, and Paco2 values induced by the procedure did not reach significance. Seven patients (15%) presented hypotension (mean blood pressure, <60 mm Hg) maintained for 120 +/- 40 secs, which required plasma expanders in three cases. Oxygen desaturation to <90% occurred in six patients (13%) during BAL. Nevertheless, the lowest Sao2 during the procedure was significantly higher than the initial Sao2 (94% +/- 4% vs. 90% +/- 2%). No patient required tracheal intubation during the 8 hrs after the procedure. BAL had an overall diagnostic yield of 65%. Because of the results obtained by using the BAL analysis, treatment was modified in 33 (72%) cases. CONCLUSION: Application of the LMA appears to be a safe and effective alternative to intubation for accomplishing FOB with BAL in immunosuppressed patients with suspected pneumonia and severe hypoxemia.

Noninvasive ventilation in immunosuppressed patients with pulmonary infiltrates, fever, and acute respiratory failure.

BACKGROUND: Avoiding intubation is a major goal in the management of respiratory failure, particularly in immunosuppressed patients. Nevertheless, there are only limited data on the efficacy of noninvasive ventilation in these high-risk patients. METHODS: We conducted a prospective, randomized trial of intermittent noninvasive ventilation, as compared with standard treatment with supplemental oxygen and no ventilatory support, in 52 immunosuppressed patients with pulmonary infiltrates, fever, and an early stage of hypoxemic acute respiratory failure. Periods of noninvasive ventilation delivered through a face mask were alternated every three hours with periods of spontaneous breathing with supplemental oxygen. The ventilation periods lasted at least 45 minutes. Decisions to intubate were made according to standard, predetermined criteria. RESULTS: The base-line characteristics of the two groups were similar; each group of 26 patients included 15 patients with hematologic cancer and neutropenia. Fewer patients in the noninvasive-ventilation group than in the standard-treatment group required endotracheal intubation (12 vs. 20, P=0.03), had serious complications (13 vs. 21, P=0.02), died in the intensive care unit (10 vs. 18, P=0.03), or died in the hospital (13 vs. 21, P=0.02). CONCLUSIONS: In selected immunosuppressed patients with pneumonitis and acute respiratory failure, early initiation of noninvasive ventilation is associated with significant reductions in the rates of endotracheal intubation and serious complications and an improved likelihood of survival to hospital discharge.

Noninvasive ventilation for acute respiratory failure. Quite low time consumption for nurses.

Methods of noninvasive pressure support ventilation (NIPSV) are not always easy to apply in patients with acute exacerbations of chronic obstructive pulmonary disease (COPD). The assistance time spent by nurses in relation to ventilatory time was prospectively studied, when NIPSV was used, in a sequential mode, in COPD patients with either acute exacerbations (58 patients, group I) or postextubation hypercapnic respiratory insufficiency (42 patients, group II) in a medical intensive care unit. During the first 24 h after enrolment, NIPSV was used for 6.7+/-3.2 h (mean+/-SD) in group I and 5.6+/-3.1 h in group II; the duration of NIPSV sessions and the nurse time consumption per session were respectively 47+/-12 and 11+/-7 min in group 1, and 46+/-12 and 11+/-6 min in group II. After the first 24 h of the study, the duration of NIPSV was 4.7+/-3.2 h x day(-1) in group I and 4.9+/-3.5 h x day(-1) in group II, and the nurse time consumption dropped significantly: the duration of NIPSV sessions and the nurse time consumption per session were respectively 44+/-10 and 7+/-4 min in group I, and 47+/-14 and 7+/-3 min in group II. Between the first 24 h and the subsequent period of 24 h, the nursing time dropped significantly (98 versus 59 min in group I (p<0.05), and 85 versus 52 min in group II (p<0.05)). There was no difference in the duration of NIPSV sessions, or in the overall assistance time per session, between the two groups of patients. In conclusion, the study seems to favour a quite low assistance time spent by nurses in relation to ventilatory time when noninvasive pressure support ventilation is used in chronic obstructive pulmonary disease patients with either acute exacerbations or postextubation hypercapnic respiratory insufficiency.

Impact of colony-stimulating factor therapy on clinical outcome and frequency rate of nosocomial infections in intensive care unit neutropenic patients.

OBJECTIVES: To determine whether the use of recombinant human granulocyte colony-stimulating factor (G-CSF, filgrastim) reduces the mortality rate and the frequency rate of nosocomial infections in neutropenic patients requiring intensive care unit (ICU) admission. DESIGN: Retrospective consecutive case series analysis. SETTING: Medical ICU of a teaching hospital. PATIENTS: We compared two groups of patients, according to whether or not they received G-CSF. In the ICU, 28 leukopenic patients received filgrastim (5 microg of body weight per day intravenously). In all these patients, G-CSF was continued until recovery from leukopenia, defined as a leukocyte count >1,000/mm3. A total of 33 ICU leukopenic patients did not receive G-CSF. End points included leukocyte count, bone marrow recovery, frequency of ICU nosocomial infections (pneumonia, urinary tract, and catheter-related infections), and mortality rate. MEASUREMENTS AND MAIN RESULTS: There were no differences in number of patients who recovered from leukopenia or in whom blood leukocyte count increased. Nosocomial infections occurred in the same percentage in both groups. The percentage of patients who died was identical in both groups. The percentage of patients with and without filgrastim therapy who recovered from leukopenia but died, was 86% and 78%, respectively. CONCLUSION: In the ICU, clinical outcome of neutropenic patients was not changed by G-CSF therapy. It is possible that G-CSF therapy may not be helpful in improving the ICU clinical outcome of neutropenic patients. Additional controlled studies designed to address this question are warranted.