Spontaneous breathing trial with pressure support on positive end-expiratory pressure and extensive use of non-invasive ventilation versus T-piece in difficult-to-wean patients from mechanical ventilation: a randomized controlled trial.

BACKGROUND: The aim of this study is to assess whether a strategy combining spontaneous breathing trial (SBT) with both pressure support (PS) and positive end-expiratory pressure (PEEP) and extended use of post-extubation non-invasive ventilation (NIV) (extensively-assisted weaning) would shorten the time until successful extubation as compared with SBT with T-piece (TP) and post-extubation NIV performed in selected patients as advocated by guidelines (standard weaning), in difficult-to-wean patients from mechanical ventilation. METHODS: The study is a single-center prospective open label, randomized controlled superiority trial with two parallel groups and balanced randomization with a 1:1 ratio. Eligible patients were intubated patients mechanically ventilated for more than 24 h who failed their first SBT using TP. In the extensively-assisted weaning group, SBT was performed with PS (7 cmH2O) and PEEP (5 cmH2O). In case of SBT success, an additional SBT with TP was performed. Failure of this SBT-TP was an additional criterion for post-extubation NIV in this group in addition to other recommended criteria. In the standard weaning group, SBT was performed with TP, and NIV was performed according to international guidelines. The primary outcome criterion was the time between inclusion and successful extubation evaluated with a Cox model with adjustment on randomization strata. RESULTS: From May 2019 to March 2023, 98 patients were included and randomized in the study (49 in each group). Four patients were excluded from the intention-to-treat population (2 in both groups); therefore, 47 patients were analyzed in each group. The extensively-assisted weaning group had a higher median age (68 [58-73] vs. 62 [55-71] yrs.) and similar sex ratio (62% male vs. 57%). Time until successful extubation was not significantly different between extensively-assisted and standard weaning groups (median, 172 [50-436] vs. 95 [47-232] hours, Cox hazard ratio for successful extubation, 0.88 [95% confidence interval: 0.55-1.42] using the standard weaning group as a reference; p = 0.60). All secondary outcomes were not significantly different between groups. CONCLUSION: An extensively-assisted weaning strategy did not lead to a shorter time to successful extubation than a standard weaning strategy. Trial registration The trial was registered on ClinicalTrials.gov (NCT03861117), on March 1, 2019, before the inclusion of the first patient. https://clinicaltrials.gov/study/NCT03861117 .

Precision of CT-derived alveolar recruitment assessed by human observers and a machine learning algorithm in moderate and severe ARDS.

BACKGROUND: Assessing measurement error in alveolar recruitment on computed tomography (CT) is of paramount importance to select a reliable threshold identifying patients with high potential for alveolar recruitment and to rationalize positive end-expiratory pressure (PEEP) setting in acute respiratory distress syndrome (ARDS). The aim of this study was to assess both intra- and inter-observer smallest real difference (SRD) exceeding measurement error of recruitment using both human and machine learning-made lung segmentation (i.e., delineation) on CT. This single-center observational study was performed on adult ARDS patients. CT were acquired at end-expiration and end-inspiration at the PEEP level selected by clinicians, and at end-expiration at PEEP 5 and 15 cmH2O. Two human observers and a machine learning algorithm performed lung segmentation. Recruitment was computed as the weight change of the non-aerated compartment on CT between PEEP 5 and 15 cmH2O. RESULTS: Thirteen patients were included, of whom 11 (85%) presented a severe ARDS. Intra- and inter-observer measurements of recruitment were virtually unbiased, with 95% confidence intervals (CI95%) encompassing zero. The intra-observer SRD of recruitment amounted to 3.5 [CI95% 2.4-5.2]% of lung weight. The human-human inter-observer SRD of recruitment was slightly higher amounting to 5.7 [CI95% 4.0-8.0]% of lung weight, as was the human-machine SRD (5.9 [CI95% 4.3-7.8]% of lung weight). Regarding other CT measurements, both intra-observer and inter-observer SRD were close to zero for the CT-measurements focusing on aerated lung (end-expiratory lung volume, hyperinflation), and higher for the CT-measurements relying on accurate segmentation of the non-aerated lung (lung weight, tidal recruitment…). The average symmetric surface distance between lung segmentation masks was significatively lower in intra-observer comparisons (0.8 mm [interquartile range (IQR) 0.6-0.9]) as compared to human-human (1.0 mm [IQR 0.8-1.3] and human-machine inter-observer comparisons (1.1 mm [IQR 0.9-1.3]). CONCLUSIONS: The SRD exceeding intra-observer experimental error in the measurement of alveolar recruitment may be conservatively set to 5% (i.e., the upper value of the CI95%). Human-machine and human-human inter-observer measurement errors with CT are of similar magnitude, suggesting that machine learning segmentation algorithms are credible alternative to humans for quantifying alveolar recruitment on CT.

Usefulness of the QuantiFERON test for the diagnosis of tubercular uveitis and the predictions of response to antituberculosis treatment.

AIMS: Few studies have evaluated the contribution of QuantiFERON test for the diagnosis of tubercular uveitis in non-endemic countries for tuberculosis (TB). The objective of the present study was to evaluate the value of the QuantiFERON test in a large cohort of patients with uveitis for both the diagnosis of tubercular uveitis and antituberculosis treatment (ATT) response prediction. METHODS: A single-centre retrospective study including consecutive adult patients with uveitis who were prescribed a QuantiFERON test between January 2003 and December 2019 was performed. Adjusted ORs (aORs) were calculated between patients with uveitis responding and not responding to ATT according to the Collaborative Ocular Tuberculosis Study (COTS) group diagnostic criteria. Sensitivity (SE), specificity (Sp), and positive and negative predictive values of the QuantiFERON test were calculated. RESULTS: A total of 1075 patients were included in the study; 178 (16.5%) were found positive using the QuantiFERON test. Among the 178 positive patients, 62 (35%) had a diagnosis of tubercular uveitis according to the updated COTS classification; all received ATT for 6 months; and 44/62 (71%) responded to ATT. A QuantiFERON test value of >2 IU/mL was associated with a greater chance of responding to ATT (aOR=36.7, 95% CI 7.2 to 185.9, p<0.001). The optimal threshold to maximise both Sp and SE for diagnosis of TB uveitis was 4 IU/mL. CONCLUSION: One-sixth of the patients diagnosed with uveitis had a positive QuantiFERON test. The QuantiFERON threshold with the optimal SE and Sp for the diagnosis of tubercular uveitis was 4 IU/mL. TRIAL REGISTRATION NUMBER: NCT03863782.

Pressure support and positive end-expiratory pressure versus T-piece during spontaneous breathing trial in difficult weaning from mechanical ventilation: study protocol for the SBT-ICU study.

BACKGROUND: Spontaneous breathing trials are performed in critically ill intubated patients in order to assess readiness to be weaned from mechanical ventilation. In patients with difficult weaning (i.e. not extubated after their first SBT), performing SBT using pressure support with or without positive end-expiratory pressure or using T-piece is debated. As ventilatory support during SBT is greater on pressure support than on T-piece and as positive end-expiratory pressure can prevent weaning-induced pulmonary oedema, we hypothesized that their combination and large use of post-extubation non-invasive ventilation may shorten the time until successful extubation as compared with T-piece, without increasing the rate of reintubation. METHODS: SBT-ICU is a monocentric prospective open labelled, randomized controlled superiority trial comparing two mechanical ventilation weaning strategies; i.e. daily spontaneous breathing trials using pressure support with positive end-expiratory pressure or T-piece. The primary outcome will be time until successful extubation (defined by as extubation, without reintubation or death within the seven following days). DISCUSSION: This paper describes the protocol of the SBT-ICU trial. Enrolment of patients in the study is ongoing. TRIAL REGISTRATION: ClinicalTrials.gov NCT03861117. Registered on March 1, 2019, before the beginning of inclusion.

Effect of High-Flow Nasal Cannula Oxygen vs Standard Oxygen Therapy on Mortality in Patients With Respiratory Failure Due to COVID-19: The SOHO-COVID Randomized Clinical Trial.

Importance: The benefit of high-flow nasal cannula oxygen (high-flow oxygen) in terms of intubation and mortality in patients with respiratory failure due to COVID-19 is controversial. Objective: To determine whether the use of high-flow oxygen, compared with standard oxygen, could reduce the rate of mortality at day 28 in patients with respiratory failure due to COVID-19 admitted in intensive care units (ICUs). Design, Setting, and Participants: The SOHO-COVID randomized clinical trial was conducted in 34 ICUs in France and included 711 patients with respiratory failure due to COVID-19 and a ratio of partial pressure of arterial oxygen to fraction of inspired oxygen equal to or below 200 mm Hg. It was an ancillary trial of the ongoing original SOHO randomized clinical trial, which was designed to include patients with acute hypoxemic respiratory failure from all causes. Patients were enrolled from January to December 2021; final follow-up occurred on March 5, 2022. Interventions: Patients were randomly assigned to receive high-flow oxygen (n = 357) or standard oxygen delivered through a nonrebreathing mask initially set at a 10-L/min minimum (n = 354). Main Outcomes and Measures: The primary outcome was mortality at day 28. There were 13 secondary outcomes, including the proportion of patients requiring intubation, number of ventilator-free days at day 28, mortality at day 90, mortality and length of stay in the ICU, and adverse events. Results: Among the 782 randomized patients, 711 patients with respiratory failure due to COVID-19 were included in the analysis (mean [SD] age, 61 [12] years; 214 women [30%]). The mortality rate at day 28 was 10% (36/357) with high-flow oxygen and 11% (40/354) with standard oxygen (absolute difference, -1.2% [95% CI, -5.8% to 3.4%]; P = .60). Of 13 prespecified secondary outcomes, 12 showed no significant difference including in length of stay and mortality in the ICU and in mortality up until day 90. The intubation rate was significantly lower with high-flow oxygen than with standard oxygen (45% [160/357] vs 53% [186/354]; absolute difference, -7.7% [95% CI, -14.9% to -0.4%]; P = .04). The number of ventilator-free days at day 28 was not significantly different between groups (median, 28 [IQR, 11-28] vs 23 [IQR, 10-28] days; absolute difference, 0.5 days [95% CI, -7.7 to 9.1]; P = .07). The most common adverse events were ventilator-associated pneumonia, occurring in 58% (93/160) in the high-flow oxygen group and 53% (99/186) in the standard oxygen group. Conclusions and Relevance: Among patients with respiratory failure due to COVID-19, high-flow nasal cannula oxygen, compared with standard oxygen therapy, did not significantly reduce 28-day mortality. Trial Registration: ClinicalTrials.gov Identifier: NCT04468126.

Response to PEEP in COVID-19 ARDS patients with and without extracorporeal membrane oxygenation. A multicenter case-control computed tomography study.

BACKGROUND: PEEP selection in severe COVID-19 patients under extracorporeal membrane oxygenation (ECMO) is challenging as no study has assessed the alveolar recruitability in this setting. The aim of the study was to compare lung recruitability and the impact of PEEP on lung aeration in moderate and severe ARDS patients with or without ECMO, using computed tomography (CT). METHODS: We conducted a two-center prospective observational case-control study in adult COVID-19-related patients who had an indication for CT within 72 h of ARDS onset in non-ECMO patients or within 72  h after ECMO onset. Ninety-nine patients were included, of whom 24 had severe ARDS under ECMO, 59 severe ARDS without ECMO and 16 moderate ARDS. RESULTS: Non-inflated lung at PEEP 5 cmH2O was significantly greater in ECMO than in non-ECMO patients. Recruitment induced by increasing PEEP from 5 to 15 cmH2O was not significantly different between ECMO and non-ECMO patients, while PEEP-induced hyperinflation was significantly lower in the ECMO group and virtually nonexistent. The median [IQR] fraction of recruitable lung mass between PEEP 5 and 15 cmH2O was 6 [4-10]%. Total superimposed pressure at PEEP 5 cmH2O was significantly higher in ECMO patients and amounted to 12 [11-13] cmH2O. The hyperinflation-to-recruitment ratio (i.e., a trade-off index of the adverse effects and benefits of PEEP) was significantly lower in ECMO patients and was lower than one in 23 (96%) ECMO patients, 41 (69%) severe non-ECMO patients and 8 (50%) moderate ARDS patients. Compliance of the aerated lung at PEEP 5 cmH2O corrected for PEEP-induced recruitment (CBABY LUNG) was significantly lower in ECMO patients than in non-ECMO patients and was linearly related to the logarithm of the hyperinflation-to-recruitment ratio. CONCLUSIONS: Lung recruitability of COVID-19 pneumonia is not significantly different between ECMO and non-ECMO patients, with substantial interindividual variations. The balance between hyperinflation and recruitment induced by PEEP increase from 5 to 15 cmH2O appears favorable in virtually all ECMO patients, while this PEEP level is required to counteract compressive forces leading to lung collapse. CBABY LUNG is significantly lower in ECMO patients, independently of lung recruitability.

Necrotizing external otitis: analysis of relapse risk factors in 66 patients managed during a 12 year period.

BACKGROUND: Necrotizing external otitis (NEO) is a severe infection of the skull base that occurs generally in the elderly and/or in diabetic recipients. There are few data in the literature about the therapeutic management of this complex bone infection. OBJECTIVES: To analyse relapses after NEO treatment completion, and to describe the clinical features of NEO. METHODS: We performed a retrospective cohort study in the Lyon regional reference centre for the management of complex bone and joint infections. Consecutive cases of NEO from 1 January 2006 to 31 December 2018 were included. The primary outcome was the relapse of NEO. Variables were analysed using Cox regression survival analysis with adjusted hazard ratio (aHR) and Kaplan-Meier curve. RESULTS: Sixty-six patients were included. Median age was 75 (IQR 69-81) years and 46 (70%) patients were diabetic. Eleven patients (17%) had temporomandibular arthritis, 10 (15%) cranial nerve paralysis, 2 (3%) cerebral thrombophlebitis, and 2 (3%) contiguous abscess. Microbiological documentation was obtained in 56 patients and revealed Pseudomonas aeruginosa in 44/56 patients (79%). Nine (14%) cases had no microbiological documentation. Antibiotic therapy was dual for 63 (95%) patients. During a median follow-up of 27 (IQR 12-40) months, 16 out of 63 (25%) patients experienced a relapse. Fungal infection was significantly associated with relapse [aHR 4.1 (95% CI 1.1-15); P = 0.03]. CONCLUSIONS: NEO is a severe bone infection, mainly (but not exclusively) caused by P. aeruginosa, which occurs in elderly and diabetic recipients. Fungal infections at baseline significantly impact the outcome.

Virological and clinical features of acute respiratory failure associated with COVID-19 in pregnancy: a case-control study.

Objective: Pregnancy is a risk factor for acute respiratory failure (ARF) following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We hypothesised that SARS-CoV-2 viral load in the respiratory tract might be higher in pregnant intensive care unit (ICU) patients with ARF than in non-pregnant ICU patients with ARF as a consequence of immunological adaptation during pregnancy. Design: Single-centre, retrospective observational case-control study. Setting: Adult level 3 ICU in a French university hospital. Participants: Eligible participants were adults with ARF associated with coronavirus disease 2019 (COVID-19) pneumonia. Main outcome measure: The primary endpoint of the study was viral load in pregnant and non-pregnant patients. Results: 251 patients were included in the study, including 17 pregnant patients. Median gestational age at ICU admission amounted to 28 + 3/7 weeks (interquartile range [IQR], 26 + 1/7 to 31 + 5/7 weeks). Twelve patients (71%) had an emergency caesarean delivery due to maternal respiratory failure. Pregnancy was independently associated with higher viral load (-4.6 ± 1.9 cycle threshold; P < 0.05). No clustering or over-represented mutations were noted regarding SARS-CoV-2 sequences of pregnant women. Emergency caesarean delivery was independently associated with a modest but significant improvement in arterial oxygenation, amounting to 32 ± 12 mmHg in patients needing invasive mechanical ventilation. ICU mortality was significantly lower in pregnant patients (0 v 35%; P < 0.05). Age, Simplified Acute Physiology Score (SAPS) II score, and acute respiratory distress syndrome were independent risk factors for ICU mortality, while pregnancy status and virological variables were not. Conclusions: Viral load was substantially higher in pregnant ICU patients with COVID-19 and ARF compared with non-pregnant ICU patients with COVID-19 and ARF. Pregnancy was not independently associated with ICU mortality after adjustment for age and disease severity.

Short- and long-term prognosis of acute critically ill patients with systemic rheumatic diseases: A retrospective multicentre study.

ABSTRACT: Patients with systemic rheumatic disease (SRD) share the risks of multi-organ flare-up, cardiovascular diseases, and immunosuppression. Such situations can lead to an acute critical illness. The present study describes the clinical features of SRD patients admitted to the intensive care unit (ICU) and their short- and long- term mortality.We performed a multicentre retrospective study in 10 French ICU in Lyon, France. Inclusion criteria were SRD diagnosis and admission for an acute organ failure. The primary endpoint was ICU mortality.A total of 271 patients were included. SRD included systemic lupus erythematosus (23.2% of included patients), vasculitis (10.7%), systemic sclerosis (10.7%), idiopathic inflammatory myopathy (6.3%), and other connective tissue disorders (rheumatoid arthritis, Sjögren and Sharp syndromes; 50.9%). Initial organ failure(s) were shock (43.5% of included patients), acute kidney injury (30.5%), and acute respiratory failure (23.2%). The cause(s) of ICU admission included sepsis (61.6%), cardiovascular events (33.9%), SRD-flare up (32.8%), and decompensations related to comorbidities (28%). The ICU mortality reached 14.3%. The factors associated with ICU mortality were chronic cardiac failure, invasive ventilation and admission in ICU for another reason than sepsis or SRD flare-up. The median follow-up after ICU discharge was 33.6 months. During follow-up, 109 patients died. The factors associated with long-term mortality included age, Charlson comorbidity index, and ICU admission for sepsis or SRD flare-up.The ICU mortality of patients with SRD was low. Sepsis was the first cause of admission. Cardiovascular events and comorbidities negatively impacted ICU mortality. Admission for sepsis or SRD flare-up exerted a negative effect on the long-term outcome.