[New therapeutic strategies in ARDS]. / Nouveautés thérapeutiques sur le SDRA.

Treatment of acute respiratory distress syndrome (ARDS) has been subject to many researches, sometimes leading to intense controversy. New findings in this field are varied. Effects on prognosis of commonly used treatments for ARDS have recently been investigated. Consistently, prone position, previously known to improve oxygenation without effect on mortality, has been shown to improve survival of the most severely hypoxemic patients. Administration of neuromuscular blocking agents in the acute phase of ARDS has been also shown to be beneficial on survival. In contrast, the exact place of extracorporeal membrane oxygenation (ECMO) in ARDS management remains to be defined despite data suggesting its possible efficiency. In addition, a new era of research has emerged with the advent of cell therapy. Mesenchymal stem cells are able to both promote alveolar epithelium repair and prevent infections. Their efficacy in animal models of ARDS still needs to be confirmed by clinical trials. Finally, other promising therapies including beta-2 adrenergic agonists and omega-3 fatty acids have shown significant limitations in large clinical studies on ARDS.

Toward improvement of knowledge of financial conflicts of interest in a large medical school in France.

INTRODUCTION: Conflict of interests (COIs) adversely affect the integrity of science and public health. The role of medical schools in the teaching and management of COIs has been highlighted by the publication of an annual evaluation of American medical schools based on their COIs policies by the American Medical Student Association (AMSA). A deontological charter was adopted by French medical schools in 2018 but its impact on COI comprehension by students and its effects on COI prevention were not evaluated. METHODS: A 10-item direct survey was conducted among about 1000 students in Paris-Cité University in order to investigate the respect of the charter regarding COIs both in the medical school and in affiliated teaching hospitals. RESULTS: Cumulative results show a satisfying respect of prevention policies regarding COIs in the medical school and hospitals despite the fact that the existence of the charter and its major aspects were insufficiently known. Disclosure of COIs by teachers was insufficient. CONCLUSION: This first direct study among students shows better results than expected according to current non-academic surveys. Moreover, this study demonstrates the feasibility of this kind of survey whose repetition should be an appropriate tool to improve the implementation of the charter within medical schools and teaching hospitals, in particular mandatory disclosure of COIs by teachers.

A model of hemodialysis after acute kidney injury in rats.

BACKGROUND: Acute kidney injury (AKI) is frequent among critically ill patients. Renal replacement therapy (RRT) is often required to deal with severe complications of AKI. This technique is however associated with side effects such as hemodynamic instability and delayed renal recovery. In this study, we aimed to describe a novel model of hemodialysis in rats with AKI and depict a dialysis membrane performance. METHODS: Eighteen Sprague-Dawley rats received 0.75% adenine-rich diet to induce AKI. After 2 weeks, nine underwent an arterio-venous extracorporeal circulation (ECC) (ECC group) for 2 h without a dialysis membrane on the circuit and nine received a hemodialysis session (HD group) for 2 h with an ECC circuit. All rats were hemodynamically monitored, and glomerular filtration rate (GFR) was measured by transcutaneous fluorescence after the injection of FITC-Sinistrin. Blood samples were collected at different time points to assess serum creatinine and serum urea concentrations and to determine the Kt/V. Sinistrin concentration was also quantified in both plasma and dialysis effluent. RESULTS: After 2 weeks of adenine-rich diet, rats exhibited a decrease in GFR. Both serum urea and serum creatinine concentrations increased in the ECC group but remained stable in the HD group. We found no significant difference in serum creatinine and serum urea concentrations between groups. At the end of experiments, mean serum urea was 36.7 mmol/l (95%CI 19.7-46.9 mmol/l) and 23.6 mmol/l (95%CI 15.2-33.5 mmol/l) in the ECC and HD groups, respectively (p = 0.15), and mean serum creatinine concentration was 158.0 µmol/l (95%CI 108.1-191.9 µmol/l) and 114.0 µmol/l (95%CI 90.2-140.9 µmol/l) in the ECC and HD groups, respectively (p = 0.11). The Kt/V of the model was estimated at 0.23. Sinistrin quantity in the ultrafiltrate raised steadily during the dialysis session. After 2 h, the median quantity was 149.2 µg (95% CI 99.7-250.3 µg). CONCLUSIONS: This hemodialysis model is an acceptable compromise between the requirement of hemodynamic tolerance which implies reducing extracorporeal blood volume (using a small dialyzer) and the demonstration that diffusion of molecules through the membrane is achieved.

[Computerized ranking test in three French universities: Staff experience and students' feedback]. / Épreuves informatisées de type ECNi: retour d'expérience sur un test multiuniversité.

BACKGROUND: The year 2016 will be pivotal for the evaluation of French medical students with the introduction of the first computerized National Ranking Test (ECNi). The SIDES, online electronic system for medical student evaluation, was created for this purpose. All the universities have already organized faculty exams but few a joint computerized ranking test at several universities simultaneously. We report our experience on the organization of a mock ECNi by universities Paris Descartes, Paris Diderot and Paris 13. METHODS: Docimological, administrative and technical working groups were created to organize this ECNi. Students in their fifth year of medical studies, who will be the first students to sit for the official ECNi in 2016, were invited to attend this mock exam that represented more than 50% of what will be proposed in 2016. A final electronic questionnaire allowed a docimological and organizational evaluation by students. An analysis of ratings and rankings and their distribution on a 1000-point scale were performed. RESULTS: Sixty-four percent of enrolled students (i.e., 654) attended the three half-day exams. No difference in total score and ranking between the three universities was observed. Students' feedback was extremely positive. Normalized over 1000 points, 99% of students were scored on 300 points only. Progressive clinical cases were the most discriminating test. CONCLUSION: The organization of a mock ECNi involving multiple universities was a docimological and technical success but required an important administrative, technical and teaching investment.

A placebo-controlled trial of selegiline (L-deprenyl) in the treatment of tardive dyskinesia.

The goal of this study was to determine whether selegiline (L-deprenyl), a selective monoamine oxidase B inhibitor and antioxidant, would improve neuroleptic-induced tardive dyskinesia (TD). Thirty-three patients with TD were randomly assigned to selegiline 10 mg/day or placebo for 6 weeks and were assessed at baseline and at weeks 1, 2, 4, and 6 for TD, parkinsonism, akathisia, depression, and positive and negative symptoms. Examinations for TD were videotaped and scored by a rater unaware of the temporal sequence of examination. Twenty-eight subjects completed at least 1 week of treatment; all five dropouts were receiving selegiline. When baseline score and gender were controlled, the group receiving selegiline displayed significantly less improvement of TD compared with the placebo group. The two treatment groups did not differ in any other outcome measure. Selegiline was less effective than placebo in reducing symptoms of TD over a 6-week trial. This may be the result of the dopamine agonist effects associated with selegiline.

Sedative effects and impaired learning and recall after single oral doses of lorazepam.

Seven healthy subjects received oral placebo, 1.5 mg lorazepam, or 3.0 mg lorazepam in a single-dose, three-way crossover study. Plasma lorazepam concentrations and subjects' self-rated sedative effects were evaluated at multiple points during 24 hours after each dose. Information acquisition and recall was studied by use of a 16-item word list at 3 and 24 hours after dosing. Lorazepam plasma concentrations were proportional to dose. Self-rated sedation was maximal 2 to 3 hours after lorazepam dosing, persisted for 8 hours, and was dose dependent in intensity; no significant sedation occurred with placebo. At 3 hours after placebo dosing, subjects learned a mean 96% of words presented during six trials; this was reduced to 79% and 62% after lorazepam, 1.5 and 3.0 mg, respectively (F = 6.2; P less than 0.02). Twenty-four hours after placebo, subjects recalled 92% of words presented the previous day, then improved to 99% after six relearning trials. After 1.5 and 3.0 mg lorazepam, however, only 52% and 44% of words were initially recalled from the previous day. Thus single oral doses of lorazepam within the therapeutic range produce dose-dependent sedation and impairment of information acquisition and recall.

A placebo-controlled trial of trihexyphenidyl in unmedicated patients with schizophrenia.

Seventeen patients with schizophrenia who had been free of medication for at least 2 months entered a placebo-controlled, random-order crossover trial of 5 mg of trihexyphenidyl twice daily for 4 weeks. Ten patients completed trials of both drug and placebo. Ratings of anticholinergic symptoms and of feeling the effects of the drug, controlled for order effects, were significantly higher at week 4 of the trihexyphenidyl trial than at week 4 of the placebo trial. Measures of psychosis, negative symptoms, depression, and liking the drug did not differ between trihexyphenidyl and placebo trials.

Kinetics and dynamics of single doses of oxazepam in the elderly: implications of absorption rate.

Five healthy elderly volunteers aged 64 to 67 years and 12 healthy young subjects aged 23 to 44 years received single 30 mg oral doses of oxazepam in two different dosage forms (two 15 mg tablets or one 30 mg capsule) on two occasions in a random crossover sequence, with at least 1 week elapsing between trials. In both age groups, rate of oxazepam absorption of the capsule form of the drug was significantly slower than that of the tablets. Peak plasma concentrations were lower and were delayed longer with the capsule form; however, the relative extent of oxazepam absorption did not differ between preparations in either age group. Clinical self-ratings in the elderly group, based on visual analog scales, were consistent with the delayed onset of sedative effects that is associated with the capsule form of administration. Kinetic comparisons in the two groups indicated a significantly prolonged oxazepam elimination half-life with the tablet (p less than .001) and with the capsule (p less than .06) and a trend (p less than .08) toward reduced oxazepam clearance in the elderly. The delayed absorption of oxazepam from the capsule was found in both the young and elderly groups.

Fluoxetine in posttraumatic stress disorder.

BACKGROUND: This study was designed to establish the efficacy of the serotonin reuptake blocker fluoxetine in the treatment of posttraumatic stress disorder (PTSD). METHOD: 64 subjects (22 women and 42 men; 31 veterans and 33 nonveterans) with PTSD entered a 5-week randomized double-blind trial comparing fluoxetine (N = 33) and placebo (N = 31). RESULTS: By Week 5 fluoxetine, but not placebo, significantly reduced overall PTSD symptomatology, as assessed by the Clinician-Administered PTSD Scale (CAPS) score. Changes were most marked in the arousal and numbing symptom subcategories. Non-VA patients responded much better than VA patients. Fluoxetine was an effective antidepressant independent of its effects on PTSD. CONCLUSION: Fluoxetine is an effective pharmacotherapeutic agent for treating PTSD and its associated features, particularly in patients without chronic treatment histories.

Correlation between simple clinical parameters and the in vitro humidification characteristics of filter heat and moisture exchangers. Groupe de Travail sur les Respirateurs.

STUDY OBJECTIVE: This study on ventilated patients in ICUs examined a large sample of heat and moisture exchanger filters (HMEFs) to determine whether simple clinical parameters are correlated with exchanger humidity output. DESIGN: A total of 594 HMEFs (18 types of HMEF) were tested in nine university hospital ICUs. PATIENTS: Each HMEF was tested on one different unselected and consecutive patient for 24 h. INTERVENTIONS: The following parameters were rated at each tracheal aspiration on a scale of 0 to 3: secretion abundance, viscosity (Visc), suction catheter adherence (Adh) to the endotracheal tube, and the amount of water condensed in the flex tube (Cond). Individual values for each type of HMEF and each variable were averaged and correlated with the humidity output (HO) of the HMEFs, values which were supplied by the manufacturers. RESULTS: There were significant correlations between HO and Cond (r=0.82, p<10(-3)), Visc (r=-0.67, p=0.002), and Adh (r=-0.56, p=0.01). A second study recorded the same variables, for three consecutive 24-h periods, using first a high-humidifying HMEF (DAR Hygrobac), followed by a low-humidifying one (Pall BB22-15), and again DAR Hygrobac. Visc and Adh were higher (p<0.05) and Cond was lower (p<0.05) with the Pall than with the DAR. CONCLUSIONS: Simple clinical parameters correlate well with the efficiency of HMEFs. The apparent water condensed in the flex tubing seems to be the best indicator of the humidifying efficiency of HMEFs.

Spontaneous pneumothorax. Comparison of thoracic drainage vs immediate or delayed needle aspiration.

In the first part of this study, 61 patients admitted for the first episode or the first recurrence of a spontaneous pneumothorax (SP) were randomly treated with thoracic drainage (TD; 28 patients) or with simple needle aspiration (NA; 33 patients). Success rate of therapy was significantly higher with TD than with NA (93%, CI 84 to 100 vs 67%, CI 51 to 83; p = 0.01). Hospital stay was similar between the two groups (7 +/- 4.6 vs 7 +/- 5.6 days), mainly because NA was delayed by 72 h in 26 patients. Recurrence rates at 3 months were 29% (CI 11 to 47%) after TD, and 14% (CI 0 to 29%) after NA (p > 0.20, NS). In the second part of the study, an additional population of 35 patients was treated by immediate NA, with a success rate of 68.5% (CI 53.5 to 83.5%), and a recurrence rate at 3 months of 30% (CI 10 to 50%). Taken together, our results indicate that NA may be proposed as a first-line treatment of SP, with a successful result in two thirds of patients and recurrence in one fifth of patients. In patients who do not heal with NA, a combined risk of TD failure and short-term recurrence of 50% may be an incentive for undelayed surgical procedures.

Nontraumatic acute anterior mediastinitis in two HIV-positive heroin addicts.

We present the cases of two young heroin addicts seropositive for HIV who had life-threatening spontaneous acute anterior mediastinitis due to Staphylococcus aureus. This was the consequence of the spreading to the mediastinum of an infection of the chest wall. Complete cure was achieved with antibiotics and surgical drainage. Spontaneous mediastinitis should arouse suspicion of the possibility of HIV infection.

Atrial septal aneurysm plus a patent foramen ovale. A predisposing factor for paradoxical embolism and refractory hypoxemia during pulmonary embolism.

We report three consecutive cases of patients who had refractory hypoxemia and paradoxical embolism during the course of pulmonary embolism. Transesophageal echocardiography showed an atrial septal aneurysm and a patent foramen ovale in all patients. The latter was detected by an early and massive passage of contrast from the right to the left atrium. We suggest that the presence of an atrial septal aneurysm plus a patent foramen ovale greatly enhances both magnitude of shunting and the risk of systemic embolism. The presence of an atrial septal aneurysm plus a patent foramen ovale should be considered and checked using transesophageal echocardiography in every patient with significant pulmonary embolism.

Use of a pulse oximeter in an adult emergency department: impact on the number of arterial blood gas analyses ordered.

STUDY OBJECTIVES: To assess the impact of pulse oximetry (SpO2) on the indications and the number of arterial blood gas (ABG) levels ordered in an adult emergency department (ED). DESIGN: A prospective study during a 2-month period in 1993 with a pulse oximeter available and a comparison with the same period in 1992 without the oximeter. SETTING: An adult medical ED of a university hospital in France. PATIENTS: All patients who underwent ABG or SpO2 measurements. INTERVENTIONS: During the prospective study, residents ordered ABG or SpO2 measurements at their discretion. The reasons for their ordering were reviewed by two independent experts who determined whether their choice was justified. The data were compared with those for 184 consecutive patients who had ABG measurements in 1992. MEASUREMENTS AND RESULTS: The study included 152 patients. SpO2 alone was used in 33 patients; ABG levels were measured in 119 patients. The use of SpO2 did not result in the ordering of fewer useful ABG determinations. One hundred and five (88%) ABG measurements were justified. There were fewer unjustified ABG determinations in 1993 when the pulse oximeter was available than in 1992 when it was not (14 of 119 vs 54 of 184; p<0.001) mainly because fewer ABG determinations were ordered for miscellaneous nonrespiratory indications (13 of 119 vs 43 of 184; p<0.01). CONCLUSION: The availability of a pulse oximeter did not affect the ordering of useful ABG measurements but allowed a significant reduction of unjustified ABG measurements. Substantial cost savings could be achieved by using SpO2 in an ED.

Prospective evaluation of the incidence of bacteremia after protected specimen brushing in ICU patients with and without pneumonia.

To test the hypothesis that the use of protected specimen brushing (PSB) via flexible bronchoscopy does not predispose to bacteremia in ICU patients, we prospectively performed aerobic and anaerobic blood cultures immediately following bronchoscopy with PSB. A total of 123 episodes in 68 consecutive patients with suspected pneumonia were analyzed. Blood cultures were negative in 110 cases (89 percent) and positive in 13 cases (11 percent) (p < 0.001). Twelve of these 13 patients with positive blood cultures had quantitative PSB specimen cultures showing nonsignificant growth (< 10(3) CFU/ml). In nine patients, the bacteria recovered from blood cultures (coagulase-negative staphylococci or sarcina) were considered nonpathogenic according to conventional criteria. Blood cultures grew a Staphylococcus aureus in two patients with previously documented staphylococcal septicemia. In one patient with no identifiable site of infection, the blood culture yielded Enterococcus faecalis. The only patient with both a positive blood culture and PSB culture results indicating pneumonia had different organisms recovered from the two samples. Blood cultures taken after PSB in the 17 other episodes of pneumonia (PSB specimen cultures > or = 10(3) CFU/ml) were negative. At the time of brushing and blood sampling for culture, none of these patients was receiving antibiotics active on the organisms found. In conclusion, the incidence of bacteremia after PSB in ICU patients seems very low even in patients with documented pneumonia. Substantial savings would result from not performing routine blood cultures after PSB.

Elastic energy as an index of right ventricular filling.

BACKGROUND: Right ventricle (RV) preload assessment remains controversial because the complexity of RV geometry is an obstacle to wall stress modeling. We developed a method to evaluate end-diastolic RV elastic energy (EL), a variable that integrates all the stretching effects of venous return and that can be easily estimated at the bedside from the area under the diastolic RV pressure-volume curve. The purpose of this study was to compare the clinical utility of EL and of the two conventional variables used to assess RV filling, ie, right atrial pressure (Pra) and RV end-diastolic volume (EDV). METHOD: We studied 26 postoperative patients who required a rapid fluid challenge. Energetics were evaluated by constructing the RV pressure-volume loop at the bedside using right heart catheterization with RV ejection fraction (EF) derivation. Correlations between RV filling and RV performance (ejection and mechanical efficiency) were studied. RV filling indexes were Pra, EDV, and EL. Indexes of RV ejection were stroke volume (SV), RV stroke work (RVSW), mechanical energy expenditure during ejection (EM), and total energy expenditure of contraction (ET). Indexes of RV mechanical efficiency were EF and the EM/ET ratio. RESULTS: Three important results were obtained. First, among RV ejection indexes, those that correlated best with RV filling indexes were EM and ET. Second, we found significant linear relationships between improved RV filling, as assessed by changes in EDV and EL, and improved RV ejection, as assessed by changes in SV, RVSW, EM, or ET. Third, changes in EDV and EL also predicted improved mechanical efficiency, as assessed by changes in EF and EM/ET. In, all situations, changes in EL yielded the strongest correlations. CONCLUSIONS: Derivation of EL is simple and appears to be the best clinical means of assessing Starling's law of the heart for the RV.

Comparison of the effects of heat and moisture exchangers and heated humidifiers on ventilation and gas exchange during weaning trials from mechanical ventilation.

Heat and moisture exchangers (HME) are increasingly used to warm and humidify inspired gases in intubated ventilated patients. But these devices add dead space that may alter the alveolar ventilation. This could impair the efficiency of spontaneous ventilation (SV) during weaning trials from mechanical ventilation. Fifteen patients were tested with an HME (Hygrobac-DAR) and a heated humidifier (HH) (Fischer-Paykel MR 450) in a random order during weaning trials in SV with inspiratory pressure support. Minute ventilation VE, tidal volume), and respiratory rate were recorded and arterial blood was sampled for blood gas analysis with each device. The HME gave a significantly greater VE than the HH (9.3 +/- 0.8 L/min vs 8.1 +/- 0.8 L/min; p < 0.005), because of increased respiratory rate (21 +/- 2/min vs 19 +/- 2/min; p < 0.05). Tidal volume was unchanged for HME and HH (470 +/- 32 mL vs 458 +/- 39 mL). The higher PaCO2 with HME than with HH (44 +/- 2 mm Hg vs 42 +/- 2 mm Hg; p < 0.005) revealed an insufficient alveolar ventilation response to the increase in dead space. Arterial Po2 rose with the HME, but not significantly above the HH values (103 +/- 6 mm Hg vs 97 +/- 6 mm Hg; p = 0.055), possibly because of a positive end-expiratory pressure effect of the HME. The need to increase VE in SV when an HME is used should be taken into account during difficult weaning from mechanical ventilation.

Bedside evaluation of efficient airway humidification during mechanical ventilation of the critically ill.

STUDY OBJECTIVE: To determine the correlation between simple rating of condensation seen in the flex-tube connecting the heating and humidifying device used with the endotracheal tube and hygrometric parameters (absolute and relative humidity and tracheal temperature) measured by psychrometry. DESIGN: Prospective randomized clinical trial. SETTING: Medical ICU of Louis Mourier Hospital, Colombes, France, a university-affiliated teaching hospital. PATIENTS: Forty-five consecutive mechanically ventilated critically ill patients. INTERVENTIONS: Patients undergoing mechanical ventilation were randomly assigned to receive humidification with one of the four heat and moisture exchangers (HMEs) tested or with a conventional heated humidifier. MEASUREMENTS: The hygrometric performances of four HMEs (BB2215, BB50, and BB100 from Pall Biomedical, Saint-Germaine-en-Laye, France; and Hygrobac-Dar from Mallinckrodt, Mirandola, Italy) and a heated humidifier (Fisher & Paykel; Auckland, New Zealand) were studied after 3 h and also after 48 h of use for the Hygrobac-Dar and correlated to a clinical visual inspection rating the amount of condensation in the flex-tube of the endotracheal tube. RESULTS: A total of 95 measurements in 45 patients were performed. The best hygrometric parameters were obtained with the heated humidifier (p < 0.001). The Hygrobac-Dar yielded significantly higher values for both humidities and tracheal temperature than the other three HMEs (p < 0.001). The performance of Hygrobac-Dar was unchanged after 48 h of use. There was a significant correlation between the condensation seen in the flex-tube and the hygrometric parameters measured by psychrometry (absolute humidity, rho = 0.7; relative humidity, rho = 0.7; tracheal temperature, rho = 0.5, p < 0.0001). CONCLUSION: In mechanically ventilated ICU patients, visual evaluation of the condensation in the flex-tube provides an estimation of the heating and humidifying efficacy of the heating and humidifying device used, thus allowing the clinician bedside monitoring of airway humidification.