Effect of Postextubation High-Flow Nasal Oxygen With Noninvasive Ventilation vs High-Flow Nasal Oxygen Alone on Reintubation Among Patients at High Risk of Extubation Failure: A Randomized Clinical Trial.

Importance: High-flow nasal oxygen may prevent postextubation respiratory failure in the intensive care unit (ICU). The combination of high-flow nasal oxygen with noninvasive ventilation (NIV) may be an optimal strategy of ventilation to avoid reintubation. Objective: To determine whether high-flow nasal oxygen with prophylactic NIV applied immediately after extubation could reduce the rate of reintubation, compared with high-flow nasal oxygen alone, in patients at high risk of extubation failure in the ICU. Design, Setting, and Participants: Multicenter randomized clinical trial conducted from April 2017 to January 2018 among 641 patients at high risk of extubation failure (ie, older than 65 years or with an underlying cardiac or respiratory disease) at 30 ICUs in France; follow-up was until April 2018. Interventions: Patients were randomly assigned to high-flow nasal oxygen alone (n = 306) or high-flow nasal oxygen alternating with NIV (n = 342) immediately after extubation. Main Outcomes and Measures: The primary outcome was the proportion of patients reintubated at day 7; secondary outcomes included postextubation respiratory failure at day 7, reintubation rates up until ICU discharge, and ICU mortality. Results: Among 648 patients who were randomized (mean [SD] age, 70 [10] years; 219 women [34%]), 641 patients completed the trial. The reintubation rate at day 7 was 11.8% (95% CI, 8.4%-15.2%) (40/339) with high-flow nasal oxygen and NIV and 18.2% (95% CI, 13.9%-22.6%) (55/302) with high-flow nasal oxygen alone (difference, -6.4% [95% CI, -12.0% to -0.9%]; P = .02). Among the 11 prespecified secondary outcomes, 6 showed no significant difference. The proportion of patients with postextubation respiratory failure at day 7 (21% vs 29%; difference, -8.7% [95% CI, -15.2% to -1.8%]; P = .01) and reintubation rates up until ICU discharge (12% vs 20%, difference -7.4% [95% CI, -13.2% to -1.8%]; P = .009) were significantly lower with high-flow nasal oxygen and NIV than with high-flow nasal oxygen alone. ICU mortality rates were not significantly different: 6% with high-flow nasal oxygen and NIV and 9% with high-flow nasal oxygen alone (difference, -2.4% [95% CI, -6.7% to 1.7%]; P = .25). Conclusions and Relevance: In mechanically ventilated patients at high risk of extubation failure, the use of high-flow nasal oxygen with NIV immediately after extubation significantly decreased the risk of reintubation compared with high-flow nasal oxygen alone. Trial Registration: ClinicalTrials.gov Identifier: NCT03121482.

High-flow nasal cannula oxygen therapy alone or with non-invasive ventilation during the weaning period after extubation in ICU: the prospective randomised controlled HIGH-WEAN protocol.

INTRODUCTION: Recent practice guidelines suggest applying non-invasive ventilation (NIV) to prevent postextubation respiratory failure in patients at high risk of extubation failure in intensive care unit (ICU). However, such prophylactic NIV has been only a conditional recommendation given the low certainty of evidence. Likewise, high-flow nasal cannula (HFNC) oxygen therapy has been shown to reduce reintubation rates as compared with standard oxygen and to be as efficient as NIV in patients at high risk. Whereas HFNC may be considered as an optimal therapy during the postextubation period, HFNC associated with NIV could be an additional means of preventing postextubation respiratory failure. We are hypothesising that treatment associating NIV with HFNC between NIV sessions may be more effective than HFNC alone and may reduce the reintubation rate in patients at high risk. METHODS AND ANALYSIS: This study is an investigator-initiated, multicentre randomised controlled trial comparing HFNC alone or with NIV sessions during the postextubation period in patients at high risk of extubation failure in the ICU. Six hundred patients will be randomised with a 1:1 ratio in two groups according to the strategy of oxygenation after extubation. The primary outcome is the reintubation rate within the 7 days following planned extubation. Secondary outcomes include the number of patients who meet the criteria for moderate/severe respiratory failure, ICU length of stay and mortality up to day 90. 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: NCT03121482.

Changes in limitations of life-sustaining treatments over time in a French intensive care unit: A prospective observational study.

BACKGROUND: Variability exists between ICUs in the limitations of therapy. Moreover practices may evolve over time. This single-center observational study aimed to compare withholding or withdrawing practices between 2012 and 2016. METHODS: For each period and patient concerned by limitations, withholding "do-not start", withholding "do-not-increase" and withdrawal measures were recorded. RESULTS: At a four-year interval, the rate of patients undergoing withholding or withdrawal rose from 10 to 23% and 4 to 7%, respectively. The proportion of patients dying in the ICU with previous limitations increased (53 to 89%), as did patients discharged alive despite withholding instructions (12 to 36%). The overall mortality (28%) was stable over time as the rate of failed resuscitation attempt declined (47 to 11%). In 2016 vs 2012, limitations started earlier following admission: 1 vs 7 days for withholding" do-not-start", 4 vs 8 for withholding "do-not-increase", 4 vs 7 for withdrawal. Notwithstanding the outcome and limitations applied, the median length of ICU stay of patients involved dropped from 13 days in 2012 to 8 days in 2016. CONCLUSION: A timely inclination to forego hopeless treatments resulted in a lower rate of failed resuscitations before death without change in global mortality.

Intravitreal Ranibizumab in Daily Clinical Practice for Age-Related Macular Degeneration: Treatment of Exudative Age-Related Macular Degeneration in Real Life.

PURPOSE: To describe the anatomical and functional outcomes in patients with exudative age-related macular degeneration (AMD) undergoing ranibizumab therapy in real-life practice. METHODS: This is a retrospective analysis of patients with exudative AMD treated with ranibizumab. Visual acuity (VA) and optic coherence tomography characteristics at baseline and at the end of the follow-up, clinical forms of the disease, delay between diagnosis and treatment as well as the number of follow-up visits and of intravitreal injections were collected. RESULTS: One hundred and seventy-nine patients (220 eyes) were followed up during a mean of 24 months. The mean delay between diagnosis and treatment was 20.3 days (SD ±16.8). VA stabilization was observed in 46.4% of eyes, 21.7% of eyes gained ≥15 ETDRS (Early Treatment Diabetic Retinopathy Study) letters and 31.9% lost ≥15 ETDRS letters. The mean central retinal thickness decreased from 380.6 µm at baseline to 295.6 µm at the final examination. A lower baseline VA score was associated with a greater gain of letters (OR 1.04, 95% CI 1.02-1.06; p < 0.001). CONCLUSION: Shortening the delays in diagnosis appears to be a key point in real-life situations.

Volume expansion in the first 4 days of shock: a prospective multicentre study in 19 French intensive care units.

PURPOSE: To describe the current practices of volume expansion in French intensive care units (ICU). METHODS: In 19 ICUs, we prospectively observed the prescription and monitoring practices of volume expansion in consecutive adult patients with shock [sustained hypotension and/or need of vasopressor therapy, associated with at least tachycardia and/or sign (s) of hypoperfusion]. Patients were included at the time of prescription of the first fluid bolus (FB). Thereafter, all the FBs administered during the 96 h following shock onset were surveyed. An FB was defined as an intravenous bolus of at least 100 ml of a blood volume expander intended to rapidly improve the patient's circulatory condition. RESULTS: We included 777 patients [age: 63 ± 15 years; female gender: 274 (35 %); simplified acute physiology score II: 55.9 ± 20.6; ICU length of stay: 6 days (interquartile range (IQR) 3-13); ICU mortality: 32.8 %] and surveyed 2,694 FBs. At enrolment mean arterial pressure was 63 mmHg (IQR 55-71). The most frequent triggers of FB were hypotension, low urine output, tachycardia, skin mottling and hyperlactataemia. Amount of fluid given at each FB was highly variable between centres. Crystalloids were used in 91 % (2,394/2,635) and synthetic colloids in 3.3 % (87/2,635) of FBs. Overall, clinicians used any kind of haemodynamic assessment (central venous pressure measurement, predictive indices of fluid responsiveness, echocardiography, cardiac output monitoring or a combination of these) in 23.6 % (635/2,694) of all FBs surveyed, with an important between-centre heterogeneity. CONCLUSIONS: High between-centre variability characterised all the aspects of FB prescription and monitoring, but overall haemodynamic exploration to help guide and monitor FB was infrequent.

Incidence and impact of skin mottling over the knee and its duration on outcome in critically ill patients.

PURPOSE: Skin mottling is frequent and can be associated with an increased mortality rate in ICU patients with septic shock. Its overall incidence in ICU and its impact on outcome is unknown. We aimed to assess the incidence of skin mottling over the knee among all critically ill patients admitted in ICU and its role on their outcome. METHODS: An observational study over a 1-year period in a 15-bed medical ICU of a teaching hospital. Skin mottling over the knee was prospectively and qualitatively assessed by trained nurses. RESULTS: Incidence of skin mottling was 29% (230 of 791 patients) in overall, and 49% (32 of 65 patients) in the subset of patients admitted for septic shock. Skin mottling was present on the day on admission in 65% of patients and persisted more than 6 h in 59% of cases. In-ICU mortality was 8% in patients without mottling, 30% in patients with short skin mottling and 40% in patients with persistent skin mottling (p < 0.01 between all groups). In the overall population, skin mottling over the knee was associated with in-ICU mortality independently from SAPS II (aOR 3.29 [95% CI, 2.08-5.19], p < 0.0001). Among patients with skin mottling over the knee, persistence of skin mottling remained associated with increased in-ICU mortality independently of organ dysfunctions at the mottling onset (OR 2.77 [95% CI, 1.34-5.72], p = 0.004). CONCLUSIONS: Skin mottling is frequent in the general population of patients admitted in ICU. Occurrence and persistence of skin mottling are independently associated with in-ICU mortality.

Cardiovascular prognosis in patients with type 2 diabetes: contribution of heart and kidney subclinical damage.

BACKGROUND: Left ventricular hypertrophy (LVH) and kidney damage (abnormal urinary albumin-to-creatinine ratio [uACR] or estimated glomerular filtration rate [eGFR]) are predictive of major cardiovascular events (MACE) in patients with type 2 diabetes (T2D) but are rarely used in cardiovascular score calculators. Our study aimed to assess their respective prognostic values for MACE and the additive information they provide to score calculators. METHODS: A total of 1298 T2D (43% women) aged 65 (SD 11) years were followed up for a median of 65 months, with MACE as a primary composite end point: cardiovascular death, nonfatal myocardial infarction, or stroke. Electrocardiogram (ECG)-derived LVH was defined using Sokolow, Gubner, and Cornell product indexes; uACR was considered as abnormal if >2.5 mg/mmol in men or >3.5 mg/mmol in women and eGFR if <60 mL/min per 1.73 m(2). RESULTS: Urinary albumin-to-creatinine ratio was higher in subjects with electrocardiographic LVH (ECG-LVH) than in subjects without (median [interquartile range] 7.61 [43.48] and 2.56 [10.53], respectively; P < .0001). After adjustment for age, history of myocardial infarction, and peripheral artery disease, ECG-LVH and kidney damage were strong predictors for MACE (adjusted hazard ratio [1.64; 95% CI 1.23-2.20], [1.90; 95% CI 1.43-2.53], and [1.85; 95% CI 1.42-2.41] for ECG-LVH, uACR, and eGFR, respectively). Net reclassification improvement was higher with the model including both ECG-LVH and uACR than models with ECG-LVH alone (P < .0001) or uACR alone (P < .0001). In addition, using cardiovascular risk calculators (Framingham score and others), we observed an additional prognostic value of ECG-LVH for each one of them. CONCLUSIONS: Electrocardiographic LVH is complementary to kidney damage for MACE prediction in T2D.