The use of non-invasive ventilation is controversial in immunocompromised patients with acute respiratory failure, whereas the use of high-flow nasal cannula oxygen therapy is growing as an ...alternative to standard oxygen. We aimed to compare outcomes of immunocompromised patients with acute respiratory failure treated with standard oxygen with those treated with high-flow nasal cannula oxygen alone or high-flow nasal cannula oxygen associated with non-invasive ventilation.
We did a post-hoc subgroup analysis in a subset of immunocompromised patients with non-hypercapnic acute respiratory failure from a multicentre, randomised, controlled trial. In the trial, patients from 23 intensive care units in France and Belgium were randomly assigned (1:1:1) to receive either standard oxygen, high-flow nasal cannula alone, or non-invasive ventilation interspaced with high-flow nasal cannula between non-invasive ventilation sessions (non-invasive ventilation group). Patients with profound neutropenia, acute-on-chronic respiratory failure, cardiogenic pulmonary oedema, shock, or altered consciousness were excluded. The primary outcome was the proportion of patients who required endotracheal intubation within 28 days after randomisation.
Of the 82 immunocompromised patients, 30 were treated with standard oxygen, 26 with high-flow nasal cannula alone, and 26 with non-invasive ventilation plus interspaced high-flow nasal cannula. 8 (31%) of 26 patients treated with high-flow nasal cannula alone, 13 (43%) of 30 patients treated with standard oxygen, and 17 (65%) of 26 patients treated with non-invasive ventilation required intubation at 28 days (p=0·04). Odds ratios (ORs) for intubation were higher in patients treated with non-invasive ventilation than in those treated with high-flow nasal cannula: OR 4·25 (95% CI 1·33-13·56). ORs were not significantly different between patients treated with high-flow nasal cannula alone and standard oxygen: OR 1·72 (0·57-5·18). After multivariable logistic regression, the two factors independently associated with endotracheal intubation and mortality were age and use of non-invasive ventilation as first-line therapy.
Non-invasive ventilation might be associated with an increased risk of intubation and mortality and should be used cautiously in immunocompromised patients with acute hypoxaemic respiratory failure.
French Ministry of Health, the French societies of intensive care (Société de Réanimation de Langue Française, SRLF) and pneumology (Société de Pneumologie de Langue Française, SPLF), La Mutuelle de Poitiers, AADAIRC (Association pour l'Assistance à Domicile Aux Insuffisants Respiratoires Chroniques), and Fisher&Paykel Healthcare.
Spontaneous-breathing trials can be performed with the use of either pressure-support ventilation (PSV) or a T-piece. Whether PSV trials may result in a shorter time to tracheal extubation than ...T-piece trials, without resulting in a higher risk of reintubation, among patients who have a high risk of extubation failure is unknown.
In this multicenter, open-label trial, we randomly assigned patients who had a high risk of extubation failure (i.e., were >65 years of age or had an underlying chronic cardiac or respiratory disease) to undergo spontaneous-breathing trials performed with the use of either PSV (with a pressure-support level of 8 cm of water and no positive end-expiratory pressure) or a T-piece. The primary outcome was the total time without exposure to invasive ventilation (reported as the number of ventilator-free days) at day 28 after the initial spontaneous-breathing trial. Secondary outcomes included extubation within 24 hours and extubation within 7 days after the initial spontaneous-breathing trial, as well as reintubation within 7 days after extubation.
A total of 969 patients (484 in the PSV group and 485 in the T-piece group) were included in the analysis. At day 28, the median number of ventilator-free days was 27 (interquartile range, 24 to 27) in the PSV group and 27 (interquartile range, 23 to 27) in the T-piece group (difference, 0 days; 95% confidence interval CI, -0.5 to 1; P = 0.31). Extubation was performed within 24 hours in 376 patients (77.7%) in the PSV group and in 350 patients (72.2%) in the T-piece group (difference, 5.5 percentage points; 95% CI, 0.01 to 10.9), and extubation was performed within 7 days in 473 patients (97.7%) and 458 patients (94.4%), respectively (difference, 3.3 percentage points; 95% CI, 0.8 to 5.9). Reintubation was performed in 72 of 481 patients (14.9%) in the PSV group and in 65 of 477 patients (13.6%) in the T-piece group (difference, 1.3 percentage points; 95% CI, -3.1 to 5.8). Cardiac or respiratory arrest was a reason for reintubation in 9 patients (3 in the PSV group and 6 in the T-piece group).
Among patients who had a high risk of extubation failure, spontaneous-breathing trials performed with PSV did not result in significantly more ventilator-free days at day 28 than spontaneous-breathing trials performed with a T-piece. (Supported by the French Ministry of Health; TIP-EX ClinicalTrials.gov number, NCT04227639.).
Background
Little attention has been paid to potential differences in prognosis between mechanically ventilated males and females in intensive care units (ICUs). We hypothesized that a sex gap in the ...risk of extubation failure in ICUs may exist.
Methods
Post hoc analysis of a large-scale clinical trial including patients at high risk of extubation failure in ICUs, with the aim of assessing the risk of extubation failure according to sex. The primary outcome was reintubation within the 7 days following extubation.
Results
Out of 641 patients, 425 (66%) were males and 216 (34%) were females. Males were more likely to be admitted for cardiac arrest and to have underlying ischemic heart disease whereas females were more likely to be admitted for coma and to have obesity. Whereas the rate of reintubation at 48 h was significantly higher in males than in females (11.0% vs. 6.0%; difference, + 5.0 95% CI, 0.2 to 9.2;
P
= 0.038), the rate of reintubation at day 7 did not significantly differ between males and females (16.7% vs. 11.1%; difference, + 5.6% 95%CI, − 0.3 to 10.8,
P
= 0.059). Using multivariable logistic regression analysis, male sex was independently associated with reintubation within the 7 days following extubation (adjusted OR 1.70 95% CI, 1.01 to 2.89;
P
= 0.048), even after adjustment on reason for admission, body-mass index, severity score, respiratory rate before extubation, and noninvasive ventilation after extubation.
Conclusion
In this post hoc analysis of a clinical trial including a homogeneous subset of patients at high risk of extubation failure, sex was independently associated with reintubation. The role of sex on outcomes should be systematically examined in future studies of critically ill patients.
The aim of this study was to evaluate the clinical efficacy of humidified oxygen via high-flow nasal cannula (HFNC) alternating with noninvasive ventilation (NIV) in acute hypoxemic respiratory ...failure (AHRF).
We performed a prospective observational study in a 12-bed ICU of a university hospital. All subjects with a PaO2 /FIO2 of ≤300 mm Hg with standard mask oxygen and a breathing frequency of > 30 breaths/min or signs of respiratory distress were included and treated with HFNC first and then NIV. Ventilatory parameters, blood gases, and tolerance were recorded during 2 consecutive sessions of NIV and HFNC. Outcome was assessed after continuation of this noninvasive strategy.
Twenty-eight subjects with AHRF were studied, including 23 (82%) with ARDS. Compared with standard oxygen therapy, PaO2 significantly increased from 83 (68-97) mm Hg to 108 (83-140) mm Hg using HFNC and to 125 (97-200) mm Hg using NIV (P<.01), whereas breathing frequency significantly decreased. HFNC was significantly better tolerated than NIV, with a lower score on the visual analog scale. The non-intubated subjects received HFNC for 75 (27-127) h and NIV for 23 (8-31) h. Intubation was required in 10 of 28 subjects (36%), including 8 of 23 subjects with ARDS (35%). After HFNC initiation, a breathing frequency of ≥30 breaths/min was an early factor associated with intubation.
HFNC was better tolerated than NIV and allowed for significant improvement in oxygenation and tachypnea compared with standard oxygen therapy in subjects with AHRF, a large majority of whom had ARDS. Thus, HFNC may be used between NIV sessions to avoid marked impairment of oxygenation.
IntroductionIn intensive care unit (ICU), the decision of extubation is a critical time because mortality is particularly high in case of reintubation. To reduce that risk, guidelines recommend to ...systematically perform a spontaneous breathing trial (SBT) before extubation in order to mimic the postextubation physiological conditions. SBT is usually performed with a T-piece disconnecting the patient from the ventilator or with low levels of pressure-support ventilation (PSV). However, work of breathing is lower during PSV than during T-piece. Consequently, while PSV trial may hasten extubation, it may also increase the risk of reintubation. We hypothesise that, compared with T-piece, SBT performed using PSV may hasten extubation without increasing the risk of reintubation.Methods and analysisThis study is an investigator-initiated, multicentre randomised controlled trial comparing T-piece vs PSV for SBTs in patients at high risk of reintubation in ICUs. Nine hundred patients will be randomised with a 1:1 ratio in two groups according to the type of SBT. The primary outcome is the number of ventilator-free days at day 28, defined as the number of days alive and without invasive mechanical ventilation between the initial SBT (day 1) and day 28. Secondary outcomes include the number of days between the initial SBT and the first extubation attempt, weaning difficulty, the number of patients extubated after the initial SBT and not reintubated within the following 72 hours, the number of patients extubated within the 7 days following the initial SBT, the number of patients reintubated within the 7 days following extubation, in-ICU length of stay and mortality in ICU, at day 28 and at day 90.Ethics and disseminationThe study has been approved by the central ethics committee ‘Ile de France V’ (2019-A02151-56) and patients will be included after informed consent. The results will be submitted for publication in peer-reviewed journals.Trial registration numberNCT04227639.
In patients with acute hypoxemic respiratory failure, noninvasive ventilation and high-flow nasal cannula oxygen are alternative strategies to conventional oxygen therapy. Endotracheal intubation is ...frequently needed in these patients with a risk of delay, and early predictors of failure may help clinicians to decide early. We aimed to identify factors associated with intubation in patients with acute hypoxemic respiratory failure treated with different noninvasive oxygenation techniques.
Post hoc analysis of a randomized clinical trial.
Twenty-three ICUs.
Patients with a respiratory rate greater than 25 breaths/min and a PaO2/FIO2 ratio less than or equal to 300 mm Hg.
Patients were treated with standard oxygen, high-flow nasal cannula oxygen, or noninvasive ventilation.
Respiratory variables one hour after treatment initiation. Under standard oxygen, patients with a respiratory rate greater than or equal to 30 breaths/min were more likely to need intubation (odds ratio, 2.76; 95% CI, 1.13-6.75; p = 0.03). One hour after high-flow nasal cannula oxygen initiation, increased heart rate was the only factor associated with intubation. One hour after noninvasive ventilation initiation, a PaO2/FIO2 ratio less than or equal to 200 mm Hg and a tidal volume greater than 9 mL/kg of predicted body weight were independent predictors of intubation (adjusted odds ratio, 4.26; 95% CI, 1.62-11.16; p = 0.003 and adjusted odds ratio, 3.14; 95% CI, 1.22-8.06; p = 0.02, respectively). A tidal volume above 9 mL/kg during noninvasive ventilation remained independently associated with 90-day mortality.
In patients with acute hypoxemic respiratory failure breathing spontaneously, the respiratory rate was a predictor of intubation under standard oxygen, but not under high-flow nasal cannula oxygen or noninvasive ventilation. A PaO2/FIO2 below 200 mm Hg and a high tidal volume greater than 9 mL/kg were the two strong predictors of intubation under noninvasive ventilation.
Aims/hypothesis
The lipid profile has not been fully investigated in individuals with peripheral artery disease (PAD). We aimed to evaluate the relationship between plasma concentrations of ...lipoproteins and the prevalence of lower-limb PAD at baseline and its incidence during follow-up in people with type 2 diabetes.
Methods
Plasma concentrations of total cholesterol, HDL-cholesterol, triacylglycerol and apolipoprotein (Apo) A-I, ApoA-II, ApoB-100 and Apo(a) were measured at baseline using colorimetric or MS methods in the SURDIAGENE cohort. Total cholesterol/HDL-cholesterol ratio, non-HDL-cholesterol and LDL-cholesterol were estimated using computation formulas. Logistic and Cox proportional hazard regression models were fitted to estimate OR or HR, with related 95% CI, for baseline prevalence or incidence of major PAD (lower-limb amputation or requirement of revascularisation) during follow-up by increasing lipoprotein tertiles, after adjustment for key confounders.
Results
Among 1468 participants (women 42%, mean ± SD age 65 ± 11 years, duration of diabetes 14 ± 10 years at baseline), 129 (8.8%) had a baseline history of major PAD. Major PAD was less prevalent at baseline in the highest (vs lowest) tertile of HDL-cholesterol (OR 0.42 95% CI 0.26, 0.71,
p
= 0.001) and ApoA-I (OR 0.39 95% CI 0.23, 0.67,
p
= 0.0007), and more frequent in the highest tertile of total cholesterol/HDL-cholesterol ratio (OR 1.95 95% CI 1.18, 3.24,
p
= 0.01). Among 1339 participants without a history of PAD at baseline, incident PAD occurred in 97 (7.2%) during a median (25th–75th percentile) duration of follow-up of 7.1 (4.4–10.7) years, corresponding to 9685 person-years and an incidence rate of 9.8 (95% CI 8.0, 12.0) per 1000 person-years. The risk of incident PAD was lower in the top (vs bottom) tertile of HDL-cholesterol (HR 0.54 95% CI 0.30, 0.95,
p
= 0.03) or ApoA-I (HR 0.50 95% CI 0.28, 0.86,
p
= 0.01) and higher in the top tertile of total cholesterol/HDL-cholesterol ratio (HR 2.81 95% CI 1.61, 5.04,
p
= 0.0002) and non-HDL-cholesterol (HR 1.80 95% CI 1.06, 3.12,
p
= 0.03).
Conclusions/interpretation
We reported independent associations between HDL-cholesterol, ApoA-I, total cholesterol/HDL-cholesterol ratio or non-HDL-cholesterol and the prevalence or the incidence of major PAD in people with type 2 diabetes. Our findings provide a picture of lipoprotein profile in people with type 2 diabetes.
Graphical abstract
Even though trimethylamine N-oxide (TMAO) has been demonstrated to interfere with atherosclerosis and diabetes pathophysiology, the association between TMAO and major adverse cardiovascular events ...(MACE) has not been specifically established in type 2 diabetes (T2D).
We examined the association of plasma TMAO concentrations with MACE and all-cause mortality in a single-center prospective cohort of consecutively recruited patients with T2D.
The study population consisted in 1463 SURDIENE participants (58% men), aged 65 ± 10 years. TMAO concentrations were significantly associated with diabetes duration, renal function, high-density lipoprotein cholesterol, soluble tumor necrosis factor receptor 1 (sTNFR1) concentrations (R2 = 0.27) and were significantly higher in patients on metformin, even after adjustment for estimated glomerular filtration rate (eGFR): 6.7 (8.5) vs 8.5 (13.6) µmol/L, respectively (PeGFR-adjusted = 0.0207). During follow-up (median duration interquartile range, 85 75 months), 403 MACE and 538 deaths were registered. MACE-free survival and all-cause mortality were significantly associated with the quartile distribution of TMAO concentrations, patients with the highest TMAO levels displaying the greatest risk of outcomes (P < 0.0001). In multivariate Cox models, compared with patients from the first 3 quartiles, those from the fourth quartile of TMAO concentration had an independently increased risk for MACE: adjusted hazard ratio (adjHR) 1.32 (1.02-1.70); P = 0.0325. Similarly, TMAO was significantly associated with mortality in multivariate analysis: adjHR 1.75 (1.17-2.09); P = 0.0124, but not when sTNFR1 and angiopoietin like 2 were considered: adjHR 1.16 (0.95-1.42); P = 0.1514.
We revealed an association between higher TMAO concentrations and increased risk of MACE and all-cause mortality, thereby opening some avenues on the role of dysbiosis in cardiovascular risk, in T2D patients.
Background Fibrillary glomerulonephritis (GN) is a rare disorder with poor renal prognosis. Therapeutic strategies, particularly the use of immunosuppressive drugs, are debated. Study Design Case ...series. Setting & Participants 27 adults with fibrillary GN referred to 15 nephrology departments in France between 1990 and 2011 were included. All patients were given renin-angiotensin system blockers and 13 received immunosuppressive therapy, including rituximab (7 patients) and cyclophosphamide (3 patients). Outcomes & Measurements Clinical and histologic features of patients and kidney disease outcome. Renal response was defined as a >50% decrease in 24-hour proteinuria with <15% decline in estimated glomerular filtration rate (eGFR). Results All patients presented with proteinuria, associated with nephrotic syndrome (41%), hematuria (73%), and hypertension (70%). Baseline median eGFR was 49 mL/min/1.73 m2 . Eight patients had a history of autoimmune disease and none had evidence of hematologic malignancy during follow-up. Light microscopic studies showed mesangial GN (70%), predominant pattern of membranous GN (19%), or membranoproliferative GN (11%). By immunofluorescence, immunoglobulin G (IgG) deposits (IgG4, 15/15; IgG1, 9/15) were polyclonal in 25 cases. Serum IgG subclass distribution was normal in the 6 patients tested. After a median 46-month follow-up, renal response occurred in 6 of 13 patients who received immunosuppressive therapy with rituximab (5 patients) or cyclophosphamide (1 patient). Of these, 5 had a mesangial or membranous light microscopic pattern, and median eGFR before therapy was 76 mL/min/1.73 m2 . In contrast, chronic kidney disease progressed in 12 of 14 patients who were not given immunosuppressive therapy, 10 of whom reached end-stage renal disease. Limitations Number of patients, retrospective study, use of multiple immunosuppressive regimens. Conclusions The therapeutic approach in fibrillary GN remains challenging. The place of immunosuppressive therapy, particularly anti–B-cell agents, needs to be assessed in larger collaborative studies.
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