Jonathan Messika

Use of High-Flow Nasal Cannula Oxygen Therapy in Subjects With ARDS: A 1-Year Observational Study

BACKGROUND: Beneficial effects of high-flow nasal cannula (HFNC) oxygen on oxygenation and respiratory parameters have been reported in a small number of subjects with acute respiratory failure (ARF). We aimed to evaluate its effect in subjects with ARDS. METHODS: This was an observational single-center study. Prospectively obtained data were retrospectively analyzed. All patients admitted over 1 y to a university hospital medicosurgical ICU were included. Classification was according to the highest ventilatory support required. HFNC indications were reviewed, and demographics, clinical characteristics, and course of subjects with ARDS according to intubation need were compared. RESULTS: Of 607 subjects admitted, 560 required ventilatory or oxygen support, among whom 180 received noninvasive ventilatory support. HFNC was used in 87 subjects and as first-line treatment in 51 subjects (29% of first-line noninvasively treated subjects), 45 of which had ARDS (PaO2/FIO2 of 137 mm Hg; 22 men, 57.9 y of age). Pneumonia accounted for 82% of ARDS causes. The intubation rate in these subjects was 40%. Higher Simplified Acute Physiology Score II (SAPS II; 46 vs 29, P = .001), occurrence of additional organ failure (76% vs 26%, P = .002), mainly hemodynamic (50% vs 7%, P = .001) or neurological (22% vs 0, P = .01), and trends toward lower PaO2/FIO2 and higher breathing frequency after HFNC initiation were evidenced in subjects who failed HFNC. Higher SAPS II scores were associated with HFNC failure in multivariate analysis. CONCLUSIONS: In daily care, over one fourth of subjects requiring noninvasive ventilatory support were treated via HFNC, with a high success rate in subjects with severe ARDS. We conclude that HFNC may be considered as first-line therapy in ARF, including patients with ARDS.

Incidence and prognosis of ventilator-associated tracheobronchitis (TAVeM): a multicentre, prospective, observational study

BACKGROUNDnVentilator-associated tracheobronchitis has been suggested as an intermediate process between tracheobronchial colonisation and ventilator-associated pneumonia in patients receiving mechanical ventilation. We aimed to establish the incidence and effect of ventilator-associated tracheobronchitis in a large, international patient cohort.nnnMETHODSnWe did a multicentre, prospective, observational study in 114 intensive care units (ICU) in Spain, France, Portugal, Brazil, Argentina, Ecuador, Bolivia, and Colombia over a preplanned time of 10 months. All patients older than 18 years admitted to an ICU who received invasive mechanical ventilation for more than 48 h were eligible. We prospectively obtained data for incidence of ventilator-associated lower respiratory tract infections, defined as ventilator-associated tracheobronchitis or ventilator-associated pneumonia. We grouped patients according to the presence or absence of such infections, and obtained data for the effect of appropriate antibiotics on progression of tracheobronchitis to pneumonia. Patients were followed up until death or discharge from hospital. To account for centre effects with a binary outcome, we fitted a generalised estimating equation model with a logit link, exchangeable correlation structure, and non-robust standard errors. This trial is registered with ClinicalTrials.gov, number NCT01791530.nnnFINDINGSnBetween Sept 1, 2013, and July 31, 2014, we obtained data for 2960 eligible patients, of whom 689 (23%) developed ventilator-associated lower respiratory tract infections. The incidence of ventilator-associated tracheobronchitis and that of ventilator-associated pneumonia at baseline were similar (320 [11%; 10·2 of 1000 mechanically ventilated days] vs 369 [12%; 8·8 of 1000 mechanically ventilated days], p=0·48). Of the 320 patients with tracheobronchitis, 250 received appropriate antibiotic treatment and 70 received inappropriate antibiotics. 39 patients with tracheobronchitis progressed to pneumonia; however, the use of appropriate antibiotic therapy for tracheobronchitis was associated with significantly lower progression to pneumonia than was inappropriate treatment (19 [8%] of 250 vs 20 [29%] of 70, p<0·0001; crude odds ratio 0·21 [95% CI 0·11-0·41]). Significantly more patients with ventilator-associated pneumonia died (146 [40%] of 369) than those with tracheobronchitis (93 [29%] of 320) or absence of ventilator-associated lower respiratory tract infections (673 [30%] of 2271, p<0·0001). Median time to discharge from the ICU for survivors was significantly longer in the tracheobronchitis (21 days [IQR 15-34]) and pneumonia (22 [13-36]) groups than in the group with no ventilator-associated lower respiratory tract infections (12 [8-20]; hazard ratio 1·65 [95% CI 1·38-1·97], p<0·0001).nnnINTERPRETATIONnThis large database study emphasises that ventilator-associated tracheobronchitis is a major health problem worldwide, associated with high resources consumption in all countries. Our findings also show improved outcomes with use of appropriate antibiotic treatment for both ventilator-associated tracheobronchitis and ventilator-associated pneumonia, underlining the importance of treating both infections, since inappropriate treatment of tracheobronchitis was associated with a higher risk of progression to pneumonia.nnnFUNDINGnNone.

Patient-important outcomes in randomized controlled trials in critically ill patients: a systematic review

BackgroundIntensivists’ clinical decision making pursues two main goals for patients: to decrease mortality and to improve quality of life and functional status in survivors. Patient-important outcomes are gaining wide acceptance in most fields of clinical research. We sought to systematically review how well patient-important outcomes are reported in published randomized controlled trials (RCTs) in critically ill patients.MethodsLiterature search was conducted to identify eligible trials indexed from January to December 2013. Articles were eligible if they reported an RCT involving critically ill adult patients. We excluded phase II, pilot and physiological crossover studies. We assessed study characteristics. All primary and secondary outcomes were collected, described and classified using six categories of outcomes including patient-important outcomes (involving mortality at any time on the one hand and quality of life, functional/cognitive/neurological outcomes assessed after ICU discharge on the other).ResultsOf the 716 articles retrieved in 2013, 112 RCTs met the inclusion criteria. Most common topics were mechanical ventilation (27%), sepsis (19%) and nutrition (17%). Among the 112 primary outcomes, 27 (24%) were patient-important outcomes (mainly mortality, 21/27) but only six (5%) were patient-important outcomes besides mortality assessed after ICU discharge (functional disabilityxa0=xa04; quality of lifexa0=xa02). Among the 598 secondary outcomes, 133 (22%) were patient-important outcomes (mainly mortality, 92/133) but only 41 (7%) were patient-important outcomes besides mortality assessed after ICU discharge (quality of lifexa0=xa020, functional disabilityxa0=xa014; neurological/cognitive performancexa0=xa05; handicapxa0=xa01; post-traumatic stressxa0=xa01). Seventy-three RCTs (65%) reported at least one patient-important outcome but only 11 (10%) reported at least one patient-important outcome besides mortality assessed after ICU discharge.ConclusionPatient-important outcomes are rarely primary outcomes in RCTs in critically ill patients published in 2013. Among them, mortality accounted for the majority. We promote the use of patient-important outcomes in critical care trials.

Five-year trends for ventilator-associated pneumonia: Correlation between microbiological findings and antimicrobial drug consumption.

The epidemiology of multidrug-resistant bacteria (MDRB) has changed significantly in European healthcare settings, with a decrease in frequency of meticillin-resistant Staphylococcus aureus and an increase in extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae. Little is known about the effects of these changes on ventilator-associated pneumonia (VAP). A retrospective 5-year trend analysis of ICU antibiotic consumption and resistance in bacteria causing VAP was undertaken. Poisson regression analysis between complete microbiological data and antibiotic consumption was performed. In total, 252 episodes of VAP in 184 patients were identified between 2007 and 2011, from which 364 causal bacteria were isolated. Enterobacteriaceae isolation rates increased significantly over this period [from 6.64 to 10.52 isolates/1000 patient-days; P=0.006], mostly due to an increase in AmpC-producing Enterobacteriaceae (APE) (2.85-4.51 isolates/1000 patient-days; P=0.013), whereas the number of episodes due to S. aureus and Pseudomonas aeruginosa remained stable. A positive association was found between the increase in APE infections and an increase in past-year antibiotic consumption: amoxicillin/clavulanic acid (P=0.003), ceftazidime and cefepime (P=0.007), carbapenems (P=0.002), fluoroquinolones (P=0.012), macrolides (P=0.002) and imidazoles (P=0.004). No such association was found for the emergence of resistance in P. aeruginosa. These results indicate a change in the epidemiology of VAP, with Enterobacteriaceae exceeding P. aeruginosa and S. aureus. Moreover, a positive correlation was observed between antibiotic consumption and the incidence of potentially MDRB such as APE. No such correlation was found for ESBL-producing Escherichia coli and antibiotic-resistant P. aeruginosa.

Impact on outcome of delayed intubation with high-flow nasal cannula oxygen: is the device solely responsible?

Dear Editor, We read with interest the study by Kang et al. [1] reporting the increase in ICU mortality of patients in whom intubation, because of high-flow nasal cannula oxygen (HFNC) failure, occurred after 48 h of use of the device. These authors must be commended for sharing their data with us, enabling others to learn and avoid pitfalls of acute respiratory failure management. While we agree with Kang et al. that HFNC bears the potential in some instances for unduly delaying intubation, a number of points in their study need to be addressed before asserting a relationship with increased mortality. First of all, if our understanding of the results is correct, only ICU mortality was found to be significantly increased, not the 28-day mortality. Since ICU length of stay was much shorter than 28 days, overall mortality was not different between the two groups. Hence, the general conclusion of the study should be qualified. Second, no indication is provided on the levels of flow used in the patients, and whether any difference was found between the two groups. This is a crucial point because one may hypothesize that HFNC may have been used sub-optimally in some patients. Indeed, deadspace washout, reduction of oxygen dilution and positive pressure provided by HFNC are dependent on the importance of flow [2]. Our attitude towards initial HFNC settings is to select the highest flow (60 L/min) to rapidly relieve dyspnea, and avoid occurrence of muscle fatigue [3–5]. It is therefore very important that Kang et al. provide readers with the precise levels of flow used in each patient. Third, no data is provided suggesting that HFNC was initiated after the same duration of respiratory failure in both groups. This may considerably impact the results. Fourth, median duration of HFNC in the[48-h group was 126 h in comparison with 10 h in the48-h group. This huge delay has been shown to considerably impact outcome during NIV, and physicians using HFNC have paid attention to not repeat the same mistake. Median duration of HFNC before intubation in different series ranged from 4 to 17.5 h [4, 5]. Close monitoring of patients under HFNC is mandatory. Leaving patients in respiratory distress for over 5 days is clearly not desirable. We found that simple clinical signs such as respiratory rate, use of accessory respiratory muscles or presence of thoraco-abdominal asynchrony were very early cues (within the first 60 min of HFNC initiation) for HFNC failure [4]. This strategy may allow using this technique even in the most severely hypoxemic patients, such as ARDS [3]. In this latter series of patients, median time to intubation was 20 h [3], noticeably shorter than the 126 h in the Kang et al. study. Finally, the electronic supplemental material of their study [1] indicates that acute-on-chronic respiratory failure was an independent risk factor for overall mortality, and that there were almost three times as many patients intubated for hypercapnic failure in the[48-h group than in the48-h one. To date, the only recommended and validated management of these patients is noninvasive ventilation. The possibility that this inadequate management may also have contributed to the excess death rather than failure of HFNC technique per se cannot be dissipated.

Decreased susceptibility to chlorhexidine affects a quarter of Escherichia coli isolates responsible for pneumonia in ICU patients

Béatrice La Combe, Alexandre Bleibtreu, Jonathan Messika, Romain Fernandes, Olivier Clermont, Catherine Branger, Typhaine Billard‐Pomares, Guilène Barnaud, Fatma Magdoud, Matthieu Eveillard, Achille Kouatchet, Sigismond Lasocki, Pierre Asfar, Stéphane Corvec, Karim Lakhal, Laurence Armand‐Lefevre, Michel Wolff, Jean‐François Timsit, Sandrine Bourdon, Jean Reignier, Stéphanie Martin, Vincent Fihman, Nicolas de Prost, Julien Bador, Pierre‐Emmanuel Charles, Julien Goret, Alexandre Boyer, Frederic Wallet, Emmanuelle Jaillette, Saad Nseir, Luce Landraud, Raymond Ruimy, Pierre‐Eric Danin, Jean Dellamonica, Julie Cremniter, Jean‐Pierre Frat, Françoise Jauréguy, Christophe Clec’h, Dominique Decré, Eric Maury, Didier Dreyfuss, Erick Denamur and Jean‐Damien Ricard

Aspergillus-induced pneumonia in adult without obvious immunodeficiency: test the burst!

Chronic granulomatous disease (CGD) is a rare primary immunodeficiency caused by a germline defect in one of the genes (CYBB, NCF1, CYBA, NCF2) encoding the NADPH oxidase 2 (NOX2) components responsible for the phagocyte oxidative burst and the production of reactive oxygen species (ROS). An early diagnosis and a prompt treatment are crucial for improving outcomes in affected patients. CGD is usually diagnosed in early childhood, and more than 95% of cases are diagnosed by the age of 5u2005years [1, 2]. However, CGD can be diagnosed late in adulthood [1–3]. Aside from residual NOX2 activity, factors underlying late diagnosis of CGD remain poorly investigated. Here, we report a case of Aspergillus-induced pneumonia rapidly extending to fatal acute respiratory distress syndrome (ARDS) revealing a late diagnosis of CGD, which was associated with a residual mitochondria-driven neutrophil extracellular trap release (NETosis) counterbalancing the lack of functional NOX2. Written informed consent was obtained from the deceased patients next-of-kin for publication of this case report and accompanying images. Unusual pathogen-driven sepsis should prompt to screen for chronic granulomatous disease, even in adult patients http://ow.ly/2FSi30iXUsa