Nebulised liposomal amphotericin-B as maintenance therapy in allergic bronchopulmonary aspergillosis: a randomised, multicentre trial.

BACKGROUND: In allergic bronchopulmonary aspergillosis (ABPA), prolonged nebulised antifungal treatment may be a strategy for maintaining remission. METHODS: We performed a randomised, single-blind, clinical trial in 30 centres. Patients with controlled ABPA after 4-month attack treatment (corticosteroids and itraconazole) were randomly assigned to nebulised liposomal amphotericin-B or placebo for 6 months. The primary outcome was occurrence of a first severe clinical exacerbation within 24 months following randomisation. Secondary outcomes included the median time to first severe clinical exacerbation, number of severe clinical exacerbations per patient, ABPA-related biological parameters. RESULTS: Among 174 enrolled patients with ABPA from March 2015 through July 2017, 139 were controlled after 4-month attack treatment and were randomised. The primary outcome occurred in 33 (50.8%) out of 65 patients in the nebulised liposomal amphotericin-B group and 38 (51.3%) out of 74 in the placebo group (absolute difference -0.6%, 95% CI -16.8- +15.6%; OR 0.98, 95% CI 0.50-1.90; p=0.95). The median (interquartile range) time to first severe clinical exacerbation was longer in the liposomal amphotericin-B group: 337 days (168-476 days) versus 177 days (64-288 days). At the end of maintenance therapy, total immunoglobulin-E and Aspergillus precipitins were significantly decreased in the nebulised liposomal amphotericin-B group. CONCLUSIONS: In ABPA, maintenance therapy using nebulised liposomal amphotericin-B did not reduce the risk of severe clinical exacerbation. The presence of some positive secondary outcomes creates clinical equipoise for further research.

Prognostic significance of central venous-to-arterial carbon dioxide difference during the first 24 hours of septic shock in patients with and without impaired cardiac function.

OBJECTIVE: To investigate the prognostic significance of central venous-to-arterial carbon dioxide difference (cv-art CO 2 gap) during septic shock in patients with and without impaired cardiac function. METHODS: We performed a prospective cohort study in 10 French intensive care units. Patients suffering from septic shock were assigned to the impaired cardiac function group ('cardiac group', n =123) if they had atrial fibrillation (AF) and/or left ventricular ejection fraction (LVEF) <50% at study entry and to the non-cardiac group ( n =240) otherwise. RESULTS: Central venous and arterial blood gases were sampled every 6 h during the first 24 h to calculate cv-art CO 2 gap. Patients in the cardiac group had a higher cv-art CO 2 gap [at study entry and 6 and 12 h (all P <0.02)] than the non-cardiac group. Patients in the cardiac group with a cv-art CO 2 gap >0.9 kPa at 12 h had a higher risk of day 28 mortality (hazard ratio=3.18; P =0.0049). Among the 59 patients in the cardiac group with mean arterial pressure (MAP) ≥65 mm Hg, central venous pressure (CVP) ≥8 mm Hg and central venous oxygen saturation (ScvO 2 ) ≥70% at 12 h, those with a high cv-art CO 2 gap (>0.9 kPa; n =19) had a higher day 28 mortality (37% vs. 13%; P =0.042). In the non-cardiac group, a high cv-art CO 2 gap was not linked to a higher risk of day 28 death, whatever the threshold value of the cv-art CO 2 gap. CONCLUSION: Patients with septic shock and with AF and/or low LVEF were more prone to a persistent high cv-art CO 2 gap, even when initial resuscitation succeeded in normalizing MAP, CVP, and ScvO 2 . In these patients, a persistent high cv-art CO 2 gap at 12 h was significantly associated with higher day 28 mortality.

[Use of high-flow nasal oxygen therapy after extubation]. / Place de l'oxygénothérapie à haut débit en post-extubation.

The decision of extubation is difficult in ICUs because in case of reintubation mortality is particularly high. High-flow nasal cannula oxygen therapy (HFNC) and noninvasive ventilation (NIV) are two respiratory supports that help to improve oxygenation, to decrease work of breathing and to decrease the risk of reintubation in selected patients. In the ICU, HFNC seems effective in patient with mild hypoxemia at time of extubation (risk of reintubation<10%) while prophylactic NIV is particularly effective in patients at high-risk of extubation failure (risk of reintubation>20%). Patients older than 65 years, those with underlying chronic cardiac or respiratory disease, or with hypercapnia are patients at high-risk easily identified at time of extubation. The best oxygenation strategy for management of post-extubation respiratory failure is unknown. HFNC has never been assessed in this setting, and NIV may have deleterious effects in patients with post-extubation respiratory failure. In postoperative patients, standard oxygen is sufficient even after major planned surgery (risk of intubation<5%), but should probably be switched to HFNC in patients with hypoxemia (risk of intubation 10-15%) and further to NIV in patients with respiratory failure with hypoxemia and clinical signs of respiratory distress (risk of intubation 50%).

[High-flow nasal oxygen in acute hypoxemic respiratory failure]. / Oxygénothérapie à haut débit nasal dans l'insuffisance respiratoire aiguë hypoxémique.

Although standard oxygen is the first-line therapy in patients with acute hypoxemic respiratory failure, high-flow nasal oxygen has gained major popularity in ICUs due to its simplicity of application, good comfort for patients, and efficiency in improving oxygenation. Physiological effects of high-flow oxygen therapy can limit the physiological consequences of acute hypoxemic respiratory failure and may mitigate the deleterious effects of high and prolonged inspiratory efforts generated by patients. Although clinical studies have reported a decreased risk of intubation with high-flow oxygen therapy as compared with conventional oxygen therapy, its benefits with regard to survival are uncertain. However, a more precise definition of acute hypoxemic respiratory failure including a classification of severity levels based on oxygenation levels is needed, the objective being to better compare the efficiency of different non-invasive oxygenation supports (conventional oxygen therapy, high-flow oxygen and non-invasive ventilation). Moreover, other clinical trials are needed to confirm the place and the benefit of these oxygenation supports, particularly high-flow nasal oxygen therapy, in acute hypoxemic respiratory failure, especially in the severe forms.

[Operating principles, physiological effects and practical issues of high-flow nasal oxygen therapy]. / Principes de fonctionnement, effets physiologiques et aspects pratiques de l'oxygénothérapie à haut débit.

First-line symptomatic treatment of acute respiratory failure (ARF) usually requires standard oxygen therapy, of which the limits have nonetheless led to the development of heated and humidified high-flow nasal oxygen therapy (HFNO). HFNO enables the delivery, through simple nasal cannula, of up to 100% of well-heated and humidified fraction of inspired oxygen (FiO2), at a maximum flow rate of 50 to 70 L/min of gas according to the devices chosen (specific or ventilator). The technical characteristics and operating principles of HFNO (coverage of the patient's spontaneous inspiratory flow, improved conditioning of the inspired gases, comfortable nasal cannula) yield a number of interdependent physiological effects that improve not only oxygenation conditions but also ventilatory mechanics. While it could be indicated in many clinical situations, including first-line hypoxemic ARF, the simplicity of HFNO implementation and the respiratory comfort it procures should in no way minimize the clinical monitoring of patients for whom endotracheal intubation may be required, and should not be unduly delayed.

[Disseminated arterial occlusions revealing bilateral venous thrombosis with paradoxical embolisms]. / Occlusions artérielles disséminées révélant une thrombose veineuse bilatérale avec embolies paradoxales.

Paradoxical embolism is a diagnosis of exclusion. Clinical triad associates deep venous thrombosis with or without pulmonary embolism, arterial embolism, and intracardiac communication with right-to-left shunt. The intracardiac communication is generally related to a patent foramen ovale (PFO). We report a 75-year-old patient, who presented with bilateral deep venous thrombosis of the legs, complicated by massive pulmonary embolism and paradoxical embolisms through a PFO. This resulted in cerebral, mesenteric, splenic and bilateral kidney infarctions. A promptly initiated anticoagulant treatment allowed a favourable outcome.

High flow nasal cannula compared with conventional oxygen therapy for acute hypoxemic respiratory failure: a systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis summarizes the safety and efficacy of high flow nasal cannula (HFNC) in patients with acute hypoxemic respiratory failure. METHODS: We performed a comprehensive search of MEDLINE, EMBASE, and Web of Science. We identified randomized controlled trials that compared HFNC to conventional oxygen therapy. We pooled data and report summary estimates of effect using relative risk for dichotomous outcomes and mean difference or standardized mean difference for continuous outcomes, with 95% confidence intervals. We assessed risk of bias of included studies using the Cochrane tool and certainty in pooled effect estimates using GRADE methods. RESULTS: We included 9 RCTs (n = 2093 patients). We found no difference in mortality in patients treated with HFNC (relative risk [RR] 0.94, 95% confidence interval [CI] 0.67-1.31, moderate certainty) compared to conventional oxygen therapy. We found a decreased risk of requiring intubation (RR 0.85, 95% CI 0.74-0.99) or escalation of oxygen therapy (defined as crossover to HFNC in the control group, or initiation of non-invasive ventilation or invasive mechanical ventilation in either group) favouring HFNC-treated patients (RR 0.71, 95% CI 0.51-0.98), although certainty in both outcomes was low due to imprecision and issues related to risk of bias. HFNC had no effect on intensive care unit length of stay (mean difference [MD] 1.38 days more, 95% CI 0.90 days fewer to 3.66 days more, low certainty), hospital length of stay (MD 0.85 days fewer, 95% CI 2.07 days fewer to 0.37 days more, moderate certainty), patient reported comfort (SMD 0.12 lower, 95% CI 0.61 lower to 0.37 higher, very low certainty) or patient reported dyspnea (standardized mean difference [SMD] 0.16 lower, 95% CI 1.10 lower to 1.42 higher, low certainty). Complications of treatment were variably reported amongst included studies, but little harm was associated with HFNC use. CONCLUSION: In patients with acute hypoxemic respiratory failure, HFNC may decrease the need for tracheal intubation without impacting mortality.

Legionnaire's pneumonia: is there really an interstitial disease?

OBJECTIVE: Legionella pneumonia is usually classified as "atypical pneumonia", which suggests a predominance of interstitial patterns in chest X-rays. Based on a selection of recent clinical cases and a brief review of the literature, the aim of the study is to clarify, how far the actual radiological findings would be consistent with these expectations. PATIENTS AND METHODS: A retrospective analysis of 18 epidemic personal cases and a review of the literature data were performed to describe the chest X-ray findings of Legionella pneumophila (LP) community acquired pneumonia. X-ray review was performed simultaneously and in consensus by two radiologists (J.P.T., E.C.) and a physician (C.G.). RESULTS: From our series, 17 patients had an abnormal chest X-ray on admission. Among these pathological X-ray cases, infiltrates were more often confluent (n=16), or patchy (n=7), rather than interstitial (n=1). Fifteen patients had infiltrates involving the lower lung fields. Bilateral distribution of abnormalities and pleural effusion were each observed in three cases. Radiological findings deteriorated between the second and seventh days following admission, particularly in the form of patchy infiltrates with pleural effusion. The review of the literature is consistent with these findings, by reporting prevalent confluent or patchy infiltrates. CONCLUSIONS: These findings are consistent with the physiopathological particularity of this affection and incite us to avoid the classification "atypical pneumonia" in radiologic terminology. This term is more appropriate for clinical and microbiological use.

[Prevalence of Acinetobacter baumannii carriage in patients of 53 French intensive care units on a given day]. / Prévalence un jour donné du portage d'Acinetobacter baumannii chez les patients de 53 réanimations françaises.

OBJECTIVE: This study was made to evaluate multiresistant Acinetobacter baumannii colonization in French intensive care units. DESIGN: We conducted a prevalence study on the carriage of A. baumannii for a one-day period in various French ICUs. On December 10, 2003, one nasal and/or rectal swab sampling was performed in 506 patients of 53 ICUs. RESULTS: Sixteen patients (3.16%) from 7 centers (13%) were colonized by A. baumannii. None of the known risk factors for colonization by multiresistant A. baumannii were identified in these patients. CONCLUSIONS: Overall, A. baumannii colonization is limited except during epidemic situations. Our study reflects the carriage of A. baumannii in ICUs on a given day. This study showed that there was no multiresistant A. baumannii epidemic clone, potentially responsible for outbreaks, present in the tested French ICUs.

[Simultaneous occlusion of the abdominal aorta and both internal carotid arteries as the presenting symptoms of left atrial myxoma]. / Occlusions simultanées de l'aorte abdominale et des deux artères carotides internes révélant un myxome de l'oreillette gauche.

Myxoma is a benign tumour but which has redoubtable embolic complications. When situated in the left atrium, the emboli obstruct, in the majority of cases, the cerebral arteries, occasionally the visceral or coronary arteries, and, very rarely, the aorta. In this case, the authors report an atypical presentation with ischaemia of the lower half of the body, associated with pulmonary oedema and deep coma. The left atrial myxoma was responsible for complete and simultaneous obstruction of the internal carotid arteries and the infra-renal abdominal aorta. This report illustrates the fact that myxoma can be responsible for massive, life-threatening, embolisation.

[High flow, humidified-reheated oxygen therapy: a new oxygenation technique for adults]. / L'oxygénothérapie humidifiée-réchauffée à haut débit : une nouvelle technique d'oxygénation chez l'adulte.

Currently conventional oxygen therapy is the first choice symptomatic treatment in the management of acute respiratory failure (ARF). However, conventional oxygen therapy has important limitations which have lead to the development of heated and humidified high-flow nasal oxygen therapy (HFNO). HFNO is an innovative technique that can deliver, through special nasal cannulae, up to 100% of the inspired fraction (FiO2) with heated and humidified oxygen at a maximum flow of 70L/min. The characteristics of this technique (overcoming the patient's spontaneous inspiratory flow, heated humidification,) and its physiological effects (no dilution of FiO2, positive end-expiratory pressure, pharyngeal dead-space washout, decrease in airway resistance), allow efficient optimization of oxygenation with better tolerance for patients. Current data, mainly observational, show that HFNO could be used particularly for the management of hypoxemic ARF, notably in the more severe forms. Indications for using HFNO, alone or in association with noninvasive ventilation, are potentially very broad and may involve different types of ARF (post-operative, post-extubation, palliative care) and even the practice of invasive technical procedures (bronchial fibroscopy). However, though current studies are very encouraging and promise a clinical benefit on patient outcomes, randomized trials are still needed to demonstrate that HFNO avoids the need for endotracheal intubation in the management of ARF.