High-flow nasal oxygen alone or alternating with non-invasive ventilation in critically ill immunocompromised patients with acute respiratory failure: a randomised controlled trial.

BACKGROUND: Although non-invasive ventilation (NIV) is recommended for immunocompromised patients with acute respiratory failure in the intensive care unit (ICU), it might have deleterious effects in the most severe patients. High-flow nasal oxygen (HFNO) alone might be an alternative method to reduce mortality. We aimed to determine whether HFNO alone could reduce the rate of mortality at day 28 compared with HFNO alternated with NIV. METHODS: FLORALI-IM is a multicentre, open-label, randomised clinical trial conducted in 29 ICUs (28 in France and one in Italy). Adult immunocompromised patients with acute respiratory failure, defined as respiratory rate of 25 breaths per min or more and a partial pressure of arterial oxygen to inspired fraction of oxygen ratio of 300 mm Hg or lower, were randomly assigned (1:1) to HFNO alone (HFNO alone group) or NIV alternating with HFNO (NIV group). Key exclusion criteria were severe hypercapnia above 50 mm Hg, patients who could strongly benefit from NIV (ie, those with underlying chronic lung disease, with cardiogenic pulmonary oedema, or who were postoperative), severe shock, impaired consciousness defined as Glasgow coma score ≤12, urgent need for intubation, do not intubate order, and contraindication to NIV. Patients were assigned using computer-generated permuted blocks and were stratified according to centre and to the type of immunosuppression using a centralised web-based management system. In the HFNO alone group, patients were continuously treated by HFNO with a gas flow rate of 60 L/min or the highest tolerated. In the NIV group, patients were treated with NIV with a first session of at least 4 h, and then by sessions for a minimal duration of 12 h a day, with a dedicated ventilator, targeting a tidal volume below 8 mL/kg of predicted bodyweight, and with a positive end-expiratory level of at least 8 cm H2O. NIV sessions were interspaced with HFNO delivered as in the HFNO alone group. The primary outcome was mortality at day 28 and was assessed in the intention-to-treat population. Secondary outcomes were mortality in the ICU, in hospital, at day 90 and at day 180, intubation at day 28, length of stay in the ICU and in hospital, number of ventilator-free days at day 28, number of oxygenation technique-free days at day 28, and efficacy and tolerance of oxygenation techniques. The trial is registered with ClinicalTrials.gov, NCT02978300, and is complete. FINDINGS: Between Jan 21, 2017 to March 4, 2019, of 497 eligible patients, 300 were randomly assigned but one patient withdrew consent, leaving 299 patients included in the intention-to-treat analysis (154 assigned to the HFNO alone group and 145 assigned to NIV group). Mortality rate at day 28 was 36% (95% CI 29·2 to 44·2; 56 of 154 patients) in the HFNO alone group and 35% (27·9 to 43·2; 51 of 145 patients) in the NIV group (absolute difference 1·2% [95% CI -9·6 to 11·9]; p=0·83). None of the other prespecified secondary outcomes were different between groups except for greater decreased discomfort after initiation of HFNO than with NIV (-4 mm on visual analogic scale [IQR -18 to 4] vs 0 mm [-16 to 17]; p=0·040). INTERPRETATION: In critically ill immunocompromised patients with acute respiratory failure, the mortality rate did not differ between HFNO alone and NIV alternating with HFNO. However, study power was limited, so results should be interpreted with caution. FUNDING: French Ministry of Health.

High-flow nasal oxygen therapy alone or with non-invasive ventilation in immunocompromised patients admitted to ICU for acute hypoxemic respiratory failure: the randomised multicentre controlled FLORALI-IM protocol.

INTRODUCTION: Non-invasive ventilation (NIV) is recommended as first-line therapy in respiratory failure of critically ill immunocompromised patients as it can decrease intubation and mortality rates as compared with standard oxygen. However, its recommendation is only conditional. Indeed, the use of NIV in this setting has been challenged recently based on results of trials finding similar outcomes with or without NIV or even deleterious effects of NIV. To date, NIV has been compared with standard oxygen but not to high-flow nasal oxygen therapy (HFOT) in immunocompromised patients. Several studies have found lower mortality rates using HFOT alone than when using HFOT with NIV sessions in patients with de novo respiratory failure, and even in immunocompromised patients. We are hypothesising that HFOT alone is more effective than HFOT with NIV sessions and reduces mortality of immunocompromised patients with acute hypoxemic respiratory failure. METHODS AND ANALYSIS: This study is an investigator-initiated, multicentre randomised controlled trial comparing HFOT alone or with NIV in immunocompromised patients admitted to intensive care unit (ICU) for severe acute hypoxemic respiratory failure. Around 280 patients will be randomised with a 1:1 ratio in two groups. The primary outcome is the mortality rate at day 28 after inclusion. Secondary outcomes include the rate of intubation in each group, length of ICU and hospital stay and mortality up to day 180. ETHICS AND DISSEMINATION: The study has been approved by the ethics committee and patients will be included after informed consent. The results will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT02978300.

Acute respiratory distress syndrome (ARDS)-associated acute cor pulmonale and patent foramen ovale: a multicenter noninvasive hemodynamic study.

INTRODUCTION: Acute cor pulmonale (ACP) and patent foramen ovale (PFO) remain common in patients under protective ventilation for acute respiratory distress syndrome (ARDS). We sought to describe the hemodynamic profile associated with either ACP or PFO, or both, during the early course of moderate-to-severe ARDS using echocardiography. METHODS: In this 32-month prospective multicenter study, 195 patients with moderate-to-severe ARDS were assessed using echocardiography during the first 48 h of admission (age: 56 (SD: 15) years; Simplified Acute Physiology Score: 46 (17); PaO2/FiO2: 115 (39); VT: 6.5 (1.7) mL/kg; PEEP: 11 (3) cmH2O; driving pressure: 15 (5) cmH2O). ACP was defined by the association of right ventricular (RV) dilatation and systolic paradoxical ventricular septal motion. PFO was detected during a contrast study using agitated saline in the transesophageal bicaval view. RESULTS: ACP was present in 36 patients, PFO in 21 patients, both PFO and ACP in 8 patients and the 130 remaining patients had neither PFO nor ACP. Patients with ACP exhibited a restricted left ventricle (LV) secondary to RV dilatation and had concomitant RV dysfunction, irrespective of associated PFO, but preserved LV systolic function. Despite elevated systolic pulmonary artery pressure (sPAP), patients with isolated PFO had a normal RV systolic function. sPAP and PaCO2 levels were significantly correlated. CONCLUSIONS: In patients under protective mechanical ventilation with moderate-to-severe ARDS, ACP was associated with LV restriction and RV failure, whether PFO was present or not. Despite elevated sPAP, PFO shunting was associated with preserved RV systolic function.

Prevalence and prognostic value of acute cor pulmonale and patent foramen ovale in ventilated patients with early acute respiratory distress syndrome: a multicenter study.

PURPOSE: We sought to determine the prevalence of and factors associated with acute cor pulmonale (ACP) and patent foramen ovale (PFO) at the early phase of acute respiratory distress syndrome (ARDS), and to assess their relation with mortality. METHODS: In this prospective multicenter study, 200 patients submitted to protective ventilation for early moderate to severe ARDS [PaO2/F(I)O2: 115 ± 39 with F(I)O2: 1; positive end-expiratory pressure (PEEP): 10.6 ± 3.1 cmH2O] underwent transthoracic (TTE) and transesophageal echocardiography (TEE) <48 h after admission. Echocardiograms were independently interpreted by two experts. Factors associated with ACP, PFO, and 28-day mortality were identified using multivariate regression analysis. RESULTS: TEE depicted ACP in 45/200 patients [22.5%; 95% confidence interval (CI) 16.9-28.9%], PFO in 31 patients (15.5%; 95% CI 10.8-21.3%), and both ACP and PFO in 9 patients (4.5%; 95% CI 2.1-8.4%). PFO shunting was small and intermittent in 27 patients, moderate and consistent in 4 patients, and large or extensive in no instances. PaCO2 >60 mmHg was strongly associated with ACP [odds ratio (OR) 3.70; 95% CI 1.32-10.38; p = 0.01]. No factor was independently associated with PFO, with only a trend for age (OR 2.07; 95% CI 0.91-4.72; p = 0.08). Twenty-eight-day mortality was 23%. Plateau pressure (OR 1.15; 95% CI 1.05-1.26; p < 0.01) and air leaks (OR 5.48; 95% CI 1.30-22.99; p = 0.02), but neither ACP nor PFO, were independently associated with outcome. CONCLUSIONS: TEE screening allowed identification of ACP in one-fourth of patients submitted to protective ventilation for early moderate to severe ARDS. PFO shunting was less frequent and never large or extensive. ACP and PFO were not related to outcome.

Comparison of silver-impregnated with standard multi-lumen central venous catheters in critically ill patients.

OBJECTIVES: To evaluate a new silver-impregnated multi-lumen central venous catheter for reducing catheter-related colonization in intensive care patients. DESIGN: Multicenter, prospective, randomized, controlled clinical study. SETTING: Ten adult intensive care units (multidisciplinary, medical and surgical, university and nonuniversity hospitals) in eight institutions. PATIENTS: A total of 577 patients who required 617 multi-lumen central venous catheters between November 2002 and April 2004 were studied. INTERVENTIONS: Intensive care adult patients requiring multi-lumen central venous catheters expected to remain in place for >or=3 days were randomly assigned to undergo insertion of silver-impregnated catheters (silver group) or standard catheters (standard group). Catheter colonization was defined as the growth of >or=1,000 colony-forming units in culture of the intravascular tip of the catheter by the vortexing method. Diagnosis of catheter-related infection was performed by an independent and blinded expert committee. RESULTS: A total of 320 catheters were studied in the silver group and 297 in the standard group. Characteristics of the patients, insertion site, duration of catheterization (median, 11 vs. 10 days), and other risk factors for infection were similar in the two groups. Colonization of the catheter occurred in 47 (14.7%) vs. 36 (12.1%) catheters in the silver and the standard groups (p = .35), for an incidence of 11.2 and 9.4 per 1,000 catheter days, respectively. Catheter-related bloodstream infection was recorded in eight (2.5%) vs. eight (2.7%) catheters in the silver and the standard groups (p = .88), for an incidence of 1.9 and 2.1 per 1,000 catheter days, respectively. CONCLUSION: The use of silver-impregnated multi-lumen catheters in adult intensive care patients is not associated with a lower rate of colonization than the use of standard multi-lumen catheters.

[Two cases of severe community-acquired pleural pneumonia due to Streptococcus pyogenes]. / Deux cas de pleuro-pneumopathies communautaires graves à Streptococcus pyogenes.

INTRODUCTION: The microorganisms incriminated in severe community-acquired pneumonia hospitalized in intensive care unit are the following: Streptococcus pneumoniae, enterobacteria isolated in aspiration-related pneumonia and less frequently intracellular bacteria in so-called atypical pneumonia (Mycoplasma pneumoniae, Chlamydia pneumoniae, Legionella pneumophila). CASE REPORTS: We report two cases of severe community-acquired pneumonia admitted in intensive care unit and due to Lancefield Group A beta hemolytic streptococcus (Streptococcus pyogenes). Despite the increased incidence of invasive streptococcal infections, this microorganism still has a rare causative role in the pathogenesis of community-acquired pneumonia. The case reports concern two young patients without any significant medical history and with many clinical, radiological and microbiological similarities. However, the prognosis was not the same because of the way the initial management has been provided. DISCUSSION: Group A beta hemolytic streptococcus could be a causative microorganism of severe and possibly fulminating community-acquired pneumonia, even in young and healthy patients as is the case with pneumococcal infections. Medical history, clinical symptoms and radiological signs should be taken into account to evoke the diagnosis and to initiate antibiotherapy early, taking into account that this microorganism is sensitive to Penicillin G.

Seven cases of fungemia with Saccharomyces boulardii in critically ill patients.

Saccharomyces boulardii (Sb) is a particular strain of Saccharomyces cerevisiae (Sc). This viable yeast is used in intensive care adult patients, delivered in packets of 500 mg, for preventing diarrhea associated with antibiotics or enteral feeding at a regimen of 1-2 g/day. Between June 1996 and October 1998, seven cases of fungemia with Sb occurred in a 12-bed intensive care unit (ICU). All the patients concerned were severely ill patients, mechanically ventilated, treated by broad spectrum antibiotics with central venous catheter and were pretreated with Sb, except for one patient. In this study, Sb was identified by specific mycologic methods and confirmed the genomic identity between isolates of blood culture and yeasts from the treatment packets, contrary to a few other reports concerning Saccharomyces species published in international literature. The hypothesis discussed for explaining these cases of Sb fungemia are: (1) an intestinal translocation of Sb administered at a high dosage in severely ill patients, (2) a contamination of the central venous catheter, especially in the patient not pretreated with Sb and (3) a massive colonization of critically ill patients by the yeast as has been reported for Candida species. We note that cases of fungemia with Sc and Sb have become more and more frequent in the international literature during the last 10 years and we do not recommend administering Sb treatment in critically ill patients.