Continuous and deep sedation until death after a decision to withdraw life-sustaining therapies in intensive care units: A national survey.

BACKGROUND: Continuous and deep sedation until death is a much highly debated end-of-life practice. France is unique in having a regulatory framework for it. However, there are no data on its practice in intensive care units (ICUs). AIM: The aim is to describe continuous and deep sedation in relation to the framework in the specific context of withdrawal of life-sustaining therapies in ICUs, that is, its decision-making process and its practice compared to other end-of-life practices in this setting. DESIGN AND SETTING: French multicenter observational study. Consecutive ICU patients who died after a decision to withdraw life-sustaining therapies. RESULTS: A total of 343 patients in 57 ICUs, 208 (60%) with continuous and deep sedation. A formalized procedure for continuous and deep sedation was available in 32% of the ICUs. Continuous and deep sedation was not the result of a collegial decision-making process in 17% of cases, and did not involve consultation with an external physician in 29% of cases. The most commonly used sedative medicines were midazolam (10 [5-18] mg h-1) and propofol (200 [120-250] mg h -1). The Richmond Agitation Sedation Scale (RASS) was -5 in 60% of cases. Analgesia was associated with sedation in 94% of cases. Compared with other end-of-life sedative practices (n = 98), medicines doses were higher with no difference in the depth of sedation. CONCLUSIONS: This study shows a poor compliance with the framework for continuous and deep sedation. It highlights the need to formalize it to improve the decision-making process and the match between the intent, the practice and the actual effect.

ICU health care workers opinion on physician-assisted-suicide and euthanasia: a French survey.

BACKGROUND: In France, physician-assisted suicide or euthanasia are not legal but are still debated. French intensive care unit (ICU) health care workers (HCWs) have an insider's perspective on the global quality of the patient's end-of-life, whether it occurs in ICU or not. However, their opinion about euthanasia/physician-assisted suicide remains unknown. The aim of this study is to investigate the opinion of French ICU HCWs about physician-assisted suicide/euthanasia. RESULTS: A total of 1149 ICU HCWs participated to a self-administered anonymous questionnaire: 411 (35.8%) physicians and 738 (64.2%) non-physicians. Among them, 76.5% indicated they were in favor of legalizing euthanasia/physician-assisted suicide. Non-physicians HCWs were significantly more in favor of the legalization of euthanasia/physician assisted suicide than physicians (87% vs 57.8% p < 0.001). Euthanasia/physician-assisted suicide of an ICU patient raised the most important difference in positive judgment between physicians and non-physicians HCWs (80.3% vs 42.2%; p < 0.001 of non-physicians and physicians, respectively). The questionnaire included three case vignettes of concrete examples which participated to the increase in the rate of response in favor of euthanasia/physician-assisted suicide legalization (76.5-82.9%; p < 0.001). CONCLUSIONS: Keeping in mind the unknown representation of our sample, ICU HCWs, particularly non physicians, would be in favor of a law legalizing euthanasia/physician-assisted suicide.

Neurologic outcome of VZV encephalitis one year after ICU admission: a multicenter cohort study.

BACKGROUND: Varicella-zoster virus (VZV) is one of the main viruses responsible of acute encephalitis. However, data on the prognosis and neurologic outcome of critically ill patients with VZV encephalitis are limited. We aimed to describe the clinical features of VZV encephalitis in the ICU and to identify factors associated with a favorable neurologic outcome. We performed a multicenter cohort study of patients with VZV encephalitis admitted in 18 ICUs in France between 2000 and 2017. Factors associated with a favorable neurologic outcome, defined by a modified Rankin Score (mRS) of 0-2 1 year after ICU admission, were identified by multivariable regression analysis. RESULTS: Fifty-five patients (29 (53%) men, median age 53 (interquartile range 36-66)) were included, of whom 43 (78%) were immunocompromised. ICU admission occurred 1 (0-3) day after the onset of neurological symptoms. Median Glasgow Coma Score at ICU admission was 12 (7-14). Cerebrospinal fluid examination displayed a median leukocyte count of 68 (13-129)/mm3, and a median protein level of 1.37 (0.77-3.67) g/L. CT scan and MRI revealed brain lesions in 30% and 66% of the cases, respectively. Invasive mechanical ventilation was implemented in 46 (84%) patients for a median duration of 13 (3-30) days. Fourteen (25%) patients died in the ICU. One year after ICU admission, 20 (36%) patients had a favorable neurologic outcome (mRS 0-2), 12 (22%) had significant disability (mRS 3-5), and 18 (33%) were deceased (lost to follow-up n = 5, 9%). On multivariable analysis, age (OR 0.92 per year, (0.88-0.97), p = 0.01), and invasive mechanical ventilation (OR 0.09 CI 95% (0.01-0.84), p = 0.03) reduced the likelihood of favorable neurologic outcome. CONCLUSION: One in every three critically ill patients with VZV encephalitis had a favorable neurologic outcome 1 year after ICU admission. Older age and invasive mechanical ventilation were associated with a higher risk of disability and death.

Impact of targeted hypothermia in expanded-criteria organ donors on recipient kidney-graft function: study protocol for a multicentre randomised controlled trial (HYPOREME).

INTRODUCTION: Expanded-criteria donors (ECDs) are used to reduce the shortage of kidneys for transplantation. However, kidneys from ECDs are associated with an increased risk of delayed graft function (DGF), a risk factor for allograft loss and mortality. HYPOREME will be a multicentre randomised controlled trial (RCT) comparing targeted hypothermia to normothermia in ECDs, in a country where the use of machine perfusion for organ storage is the standard of care. We hypothesise that hypothermia will decrease the incidence of DGF. METHODS AND ANALYSIS: HYPOREME is a multicentre RCT comparing the effect on kidney function in recipients of targeted hypothermia (34°C-35°C) and normothermia (36.5°C-37.5°C) in the ECDs. The temperature intervention starts from randomisation and is maintained until aortic clamping in the operating room. We aim to enrol 289 ECDs in order to analyse the kidney function of 516 recipients in the 53 participating centres. The primary outcome is the occurrence of DGF in kidney recipients, defined as a requirement for renal replacement therapy within 7 days after transplantation (not counting a single session for hyperkalemia during the first 24 hours). Secondary outcomes include the proportion of patients with individual organs transplanted in each group; the number of organs transplanted from each ECD and the vital status and kidney function of the recipients 7 days, 28 days, 3 months and 1 year after transplantation. An interim analysis is planned after the enrolment of 258 kidney recipients. ETHICS AND DISSEMINATION: The trial was approved by the ethics committee of the French Intensive Care Society (CE-SRLF-16-07) on 26 April 2016 and by the competent French authorities on 20 April 2016 (Comité de Protection des Personnes-TOURS-Région Centre-Ouest 1, registration #2016-S3). Findings will be published in peer-reviewed journals and presented during national and international scientific meetings. TRIAL REGISTRATION NUMBER: NCT03098706.

Critical pathways for controlled donation after circulatory death in France.

INTRODUCTION: In 2015, France authorised controlled donation after circulatory death (cDCD) according to a nationally approved protocol. The aim of this study is to provide an overview from the perspective of critical care specialists of cDCD. The primary objective is to assess how the organ donation procedure affects the withdrawal of life-sustaining therapies (WLST) process. The secondary objective is to assess the impact of cDCD donors' diagnoses on the whole process. MATERIAL AND METHODS: This 2015-2019 prospective observational multicentre study evaluated the WLST process in all potential cDCD donors identified nationwide, comparing 2 different sets of subgroups: 1- those whose WLST began after organ donation was ruled out vs. while it was still under consideration; 2- those with a main diagnosis of post-anoxic brain injury (PABI) vs. primary brain injury (PBI) at the time of the WLST decision. RESULTS: The study analysed 908 potential cDCD donors. Organ donation remained under consideration at WLST initiation for 54.5% of them with longer intervals between their WLST decision and its initiation (2 [1-4] vs. 1 [1-2] days, P < 0.01). Overall, 60% had post-anoxic brain injury. Time from ICU admission to WLST decision was longer for primary brain injury donors (10 [4-21] vs. 6 [4-9] days, P < 0.01). Median time to death (agonal phase) was 15 [15-20] min. CONCLUSIONS: French cDCD donors are mostly related to post-anoxic brain injury. The organ donation process does not accelerate WLST decision but increases the interval between the WLST decision and its initiation.

Renal Replacement Therapy for Acute Kidney Injury in French Intensive Care Units: A Nationwide Survey of Practices.

BACKGROUND: The frequency of acute kidney injury (AKI) can be as high as 50% in the intensive care unit (ICU). Despite the publication of national guidelines in France in 2015 for the use of RRT, there are no data describing the implementation of these recommendations in real-life. METHODS: We performed a nationwide survey of practices from November 15, 2019, to January 24, 2020, in France. An electronic questionnaire based on the items recommended in the national guidelines was sent using an online survey platform, to the chiefs of all ICUs in France. The questionnaire comprised a section for the Department Chief about local organization and facilities, and a second section destined for individual physicians about their personal practices. RESULTS: We contacted the Department Chief in 356 eligible ICUs, of whom 88 (24.7%) responded regarding their ICU organization. From these 88 ICUs, 232/285 physicians (82%) completed the questionnaire regarding individual practices. The practices reported by respondent physicians were as follows: intermittent RRT was first-line choice in >75% in a patient with single organ (kidney) failure at the acute phase, whereas continuous RRT was predominant (>75%) in patients with septic shock or multi-organ failure. Blood and dialysate flow for intermittent RRT were 200-300 mL/min and 400-600 mL/min, respectively. The dose of dialysis for continuous RRT was 25-35 mL/kg/h (65%). Insertion of the dialysis catheter was mainly performed by the resident under echographic guidance, in the right internal jugular vein. The most commonly used catheter lock was citrate (53%). The most frequently cited criterion for weaning from RRT was diuresis, followed by a drop in urinary markers (urea and creatinine). CONCLUSION: This study shows a satisfactory level of reported compliance with French guidelines and recent scientific evidence among ICU physicians regarding initiation of RRT for AKI in the ICU.

ß Agonist Delivery by High-Flow Nasal Cannula During COPD Exacerbation.

BACKGROUND: Whereas high-flow nasal cannula (HFNC) oxygen therapy is increasingly used in patients with exacerbation of COPD, the effectiveness of ß 2 agonist nebulization through HFNC has been poorly assessed. We hypothesized that salbutamol vibrating-mesh nebulization through HFNC improves pulmonary function tests in subjects with COPD. METHODS: We conducted a physiological crossover study including subjects admitted to the ICU for severe exacerbation of COPD. After subject improvement allowing a 3-h washout period without bronchodilator, pulmonary function tests were performed while breathing through HFNC alone and after salbutamol vibrating-mesh nebulization through HFNC. The primary end point consisted in the changes in FEV1 before and after salbutamol nebulization. Secondary end points included the changes in FVC, peak expiratory flow (PEF), airway resistance, and clinical parameters. RESULTS: Among the 15 subjects included, mean (SD) FEV1 significantly increased after salbutamol nebulization from 931 mL (383) to 1,019 (432), mean difference +87 mL (95% CI 30-145) (P = .006). Similarly, FVC and PEF significantly increased, +174 mL (95% CI 66-282) (P = .004) and +0.3 L/min (95% CI 0-0.6) (P = .037), respectively. Airway resistances and breathing frequency did not significantly differ, whereas heart rate significantly increased after nebulization. CONCLUSIONS: In subjects with severe exacerbation of COPD, salbutamol vibrating-mesh nebulization through HFNC induced a significant bronchodilator effect with volume and flow improvement.

Beneficial Effects of Noninvasive Ventilation after Extubation in Obese or Overweight Patients: A Post Hoc Analysis of a Randomized Clinical Trial.

Rationale: Although noninvasive ventilation (NIV) may prevent reintubation in patients at high risk of extubation failure in ICUs, this oxygenation strategy has not been specifically assessed in obese patients. Objectives: We hypothesized that NIV may decrease the risk of reintubation in obese patients compared with high-flow nasal oxygen. Methods:Post hoc analysis of a multicenter randomized controlled trial (not prespecified) comparing NIV alternating with high-flow nasal oxygen versus high-flow nasal oxygen alone after extubation, with the aim of assessing NIV effects according to patient body mass index (BMI). Measurements and Main Results: Among 623 patients at high risk of extubation failure, 206 (33%) were obese (BMI ⩾ 30 kg/m2), 204 (33%) were overweight (25 kg/m2 ⩽ BMI < 30 kg/m2), and 213 (34%) were normal or underweight (BMI < 25 kg/m2). Significant heterogeneity of NIV effects on the rate of reintubation was found according to BMI (Pinteraction = 0.007). Reintubation rates at Day 7 were significantly lower with NIV alternating with high-flow nasal oxygen than with high-flow nasal oxygen alone in obese or overweight patients: 7% (15/204) versus 20% (41/206) (difference, -13% [95% confidence interval, -19 to -6]; P = 0.0002), whereas it did not significantly differ in normal or underweight patients. In-ICU mortality was significantly lower with NIV than with high-flow nasal oxygen alone in obese or overweight patients (2% vs. 9%; difference, -6% [95% confidence interval, -11 to -2]; P = 0.006). Conclusions: Prophylactic NIV alternating with high-flow nasal oxygen immediately after extubation significantly decreased the risk of reintubation and death compared with high-flow nasal oxygen alone in obese or overweight patients at high risk of extubation failure. By contrast, NIV was not effective in normal or underweight patients. Clinical trial registered with www.clinicaltrials.gov (NCT03121482).

Endotoxin Mass Concentration in Plasma Is Associated With Mortality in a Multicentric Cohort of Peritonitis-Induced Shock.

Objectives: To investigate the association of plasma LPS mass with mortality and inflammation in patients with peritonitis-induced septic shock (SS). Design: Longitudinal endotoxin and inflammatory parameters in a multicentric cohort of SS. Patients: Protocolized post-operative parameters of 187 SS patients collected at T1 (12 h max post-surgery) and T4 (24 h after T1). Intervention: Post-hoc analysis of ABDOMIX trial. Measurements and Results: Plasma concentration of LPS mass as determined by HPLC-MS/MS analysis of 3-hydroxymyristate, activity of phospholipid transfer protein (PLTP), lipids, lipoproteins, IL-6, and IL-10. Cohort was divided in low (LLPS) and high (HLPS) LPS levels. The predictive value for mortality was tested by multivariate analysis. HLPS and LLPS had similar SAPSII (58 [48.5; 67]) and SOFA (8 [6.5; 9]), but HLPS showed higher death and LPS to PLTP ratio (p < 0.01). LPS was stable in HLPS, but it increased in LLPS with a greater decrease in IL-6 (p < 0.01). Dead patients had a higher T1 LPS (p = 0.02), IL-6 (<0.01), IL-10 (=0.01), and day 3 SOFA score (p = 0.01) than survivors. In the group of SAPSII > median, the risk of death in HLPS (38%) was higher than in LLPS (24%; p < 0.01). The 28-day death was associated only with SAPSII (OR 1.06 [1.02; 1.09]) and HLPS (OR 2.47 [1; 6.11]) in the multivariate model. In HLPS group, high PLTP was associated with lower plasma levels of IL-6 (p = 0.02) and IL-10 (p = 0.05). Conclusions: Combination of high LPS mass concentration and high SAPS II is associated with elevated mortality in peritonitis-induced SS patients.

Noninvasive ventilation vs. high-flow nasal cannula oxygen for preoxygenation before intubation in patients with obesity: a post hoc analysis of a randomized controlled trial.

BACKGROUND: Critically ill patients with obesity may have an increased risk of difficult intubation and subsequent severe hypoxemia. We hypothesized that pre-oxygenation with noninvasive ventilation before intubation as compared with high-flow nasal cannula oxygen may decrease the risk of severe hypoxemia in patients with obesity. METHODS: Post hoc subgroup analysis of critically ill patients with obesity (body mass index ≥ 30 kg·m-2) from a multicenter randomized controlled trial comparing preoxygenation with noninvasive ventilation and high-flow nasal oxygen before intubation of patients with acute hypoxemic respiratory failure (PaO2/FiO2 < 300 mm Hg). The primary outcome was the occurrence of severe hypoxemia (pulse oximetry < 80%) during the intubation procedure. RESULTS: Among the 313 patients included in the original trial, 91 (29%) had obesity with a mean body mass index of 35 ± 5 kg·m-2. Patients with obesity were more likely to experience an episode of severe hypoxemia during intubation procedure than patients without obesity: 34% (31/91) vs. 22% (49/222); difference, 12%; 95% CI 1 to 23%; P = 0.03. Among patients with obesity, 40 received preoxygenation with noninvasive ventilation and 51 with high-flow nasal oxygen. Severe hypoxemia occurred in 15 patients (37%) with noninvasive ventilation and 16 patients (31%) with high-flow nasal oxygen (difference, 6%; 95% CI - 13 to 25%; P = 0.54). The lowest pulse oximetry values during intubation procedure were 87% [interquartile range, 77-93] with noninvasive ventilation and 86% [78-92] with high-flow nasal oxygen (P = 0.98). After multivariable analysis, factors independently associated with severe hypoxemia in patients with obesity were intubation difficulty scale > 5 points and respiratory primary failure as reason for admission. CONCLUSIONS: Patients with obesity and acute hypoxemic respiratory failure had an increased risk of severe hypoxemia during intubation procedure as compared to patients without obesity. However, preoxygenation with noninvasive ventilation may not reduce this risk compared with high-flow nasal oxygen. Trial registration Clinical trial number: NCT02668458 ( http://www.clinicaltrials.gov ).

Non-invasive ventilation versus high-flow nasal oxygen for postextubation respiratory failure in ICU: a post-hoc analysis of a randomized clinical trial.

BACKGROUND: In intensive care units (ICUs), patients experiencing post-extubation respiratory failure have poor outcomes. The use of noninvasive ventilation (NIV) to treat post-extubation respiratory failure may increase the risk of death. This study aims at comparing mortality between patients treated with NIV alternating with high-flow nasal oxygen or high-flow nasal oxygen alone. METHODS: Post-hoc analysis of a multicenter, randomized, controlled trial focusing on patients who experienced post-extubation respiratory failure within the 7 days following extubation. Patients were classified in the NIV group or the high-flow nasal oxygen group according to oxygenation strategy used after the onset of post-extubation respiratory failure. Patients reintubated within the first hour after extubation and those promptly reintubated without prior treatment were excluded. The primary outcome was mortality at day 28 after the onset of post-extubation respiratory failure. RESULTS: Among 651 extubated patients, 158 (25%) experienced respiratory failure and 146 were included in the analysis. Mortality at day 28 was 18% (15/84) using NIV alternating with high-flow nasal oxygen and 29% (18/62) with high flow nasal oxygen alone (difference, - 11% [95% CI, - 25 to 2]; p = 0.12). Among the 46 patients with hypercapnia at the onset of respiratory failure, mortality at day 28 was 3% (1/33) with NIV and 31% (4/13) with high-flow nasal oxygen alone (difference, - 28% [95% CI, - 54 to - 6]; p = 0.006). The proportion of patients reintubated 48 h after the onset of post-extubation respiratory failure was 44% (37/84) with NIV and 52% (32/62) with high-flow nasal oxygen alone (p = 0.21). CONCLUSIONS: In patients with post-extubation respiratory failure, NIV alternating with high-flow nasal oxygen might not increase the risk of death. Trial registration number The trial was registered at http://www.clinicaltrials.gov with the registration number NCT03121482 the 20th April 2017.

Role of sleep on respiratory failure after extubation in the ICU.

BACKGROUND: Sleep had never been assessed immediately after extubation in patients still in the ICU. However, sleep deprivation may alter respiratory function and may promote respiratory failure. We hypothesized that sleep alterations after extubation could be associated with an increased risk of post-extubation respiratory failure and reintubation. We conducted a prospective observational cohort study performed at the medical ICU of the university hospital of Poitiers in France. Patients at high-risk of extubation failure (> 65 years, with any underlying cardiac or lung disease, or intubated > 7 days) were included. Patients intubated less than 24 h, with central nervous or psychiatric disorders, continuous sedation, neuroleptic medication, or uncooperative were excluded. Sleep was assessed by complete polysomnography just following extubation including the night. The main objective was to compare sleep between patients who developed post-extubation respiratory failure or required reintubation and the others. RESULTS: Over a 3-year period, 52 patients had complete polysomnography among whom 12 (23%) developed post-extubation respiratory failure and 8 (15%) required reintubation. Among them, 10 (19%) had atypical sleep, 15 (29%) had no deep sleep, and 33 (63%) had no rapid eye movement (REM) sleep. Total sleep time was 3.2 h in median [interquartile range, 2.0-4.4] in patients who developed post-extubation respiratory failure vs. 2.0 [1.1-3.8] in those who were successfully extubated (p = 0.34). Total sleep time, and durations of deep and REM sleep stages did not differ between patients who required reintubation and the others. Reintubation rates were 21% (7/33) in patients with no REM sleep and 5% (1/19) in patients with REM sleep (difference, - 16% [95% CI - 33% to 6%]; p = 0.23). CONCLUSIONS: Sleep assessment by polysomnography after extubation showed a dramatically low total, deep and REM sleep time. Sleep did not differ between patients who were successfully extubated and those who developed post-extubation respiratory failure or required reintubation.

High risk of pulmonary embolism in acute respiratory distress syndrome related to COVID-19: an observational controlled-cohort study.

BACKGROUND: COVID-19 may induce endovascular injury of pulmonary vessels and could be associated with increased risk of pulmonary embolism. The main objective was to compare the incidence of pulmonary embolism in patients with acute respiratory distress syndrome (ARDS) related to COVID-19 versus patients with pulmonary ARDS unrelated to COVID-19. METHODS: This is an observational controlled-cohort study performed at a single center of a university teaching hospital in France. The incidence of pulmonary embolism was prospectively assessed using computed tomography pulmonary angiography (CTPA) in patients with ARDS related to COVID-19 and compared to patients from a 3-year historical cohort of patients with pulmonary ARDS unrelated to COVID-19. In patients with ARDS related to COVID-19, CTPA was performed approximately 7 days after intubation or earlier in case of respiratory or hemodynamic worsening. RESULTS: CTPA was performed in 29 out of the 42 patients (69%) with ARDS related to COVID-19 and in 51 out of the 156 patients (33%) from the historical cohort of patients with pulmonary ARDS unrelated to COVID-19. Incidence of pulmonary embolism was 40% (17/42) in patients with ARDS related to COVID-19 and 3% (5/156) in the historical cohort (P=0.001). The proportion of patients with pulmonary embolism among all patients who had CTPA was 59% (17/29) in patients with ARDS related to COVID-19 and 10% (5/51) in the historical cohort (P=0.0001). After adjustment on the interval between ICU admission and computed tomography, COVID-19 remained independently associated with pulmonary embolism. CONCLUSIONS: Pulmonary embolism was particularly frequent in patients with ARDS related to COVID-19, thereby suggesting that CTPA should be systematically performed in these patients.

Sleep deprivation reduces vagal tone during an inspiratory endurance task in humans.

STUDY OBJECTIVES: Sleep deprivation alters inspiratory endurance by reducing inspiratory motor output. Vagal tone is involved in exercise endurance. This study aimed to investigate the effect of sleep deprivation on vagal tone adaptation in healthy subjects performing an inspiratory effort. METHODS: Vagal tone was assessed using Heart Rate Variability normalized units of frequency domain component HF (high frequency) before, at the start, and the end of an inspiratory loading trial performed until exhaustion by 16 volunteers after one night of sleep deprivation and one night of normal sleep, where sleep deprivation reduced the inspiratory endurance by half compared to the normal sleep condition (30 min vs 60 min). RESULTS: At rest, heart rate was similar in sleep deprivation and normal sleep conditions. In normal sleep condition, heart rate increased during inspiratory loading task; this increase was greater in sleep deprivation condition. In normal sleep condition, vagal tone increased at the beginning of the trial. This vagal tone increase was absent in sleep deprivation condition. CONCLUSIONS: Sleep deprivation abolished vagal tone response to inspiratory load, possibly contributing to a higher heart rate during the trial and to a reduced inspiratory endurance. CLINICAL TRIAL REGISTRATION: NCT02725190.

Non-invasive ventilation alternating with high-flow nasal oxygen versus high-flow nasal oxygen alone after extubation in COPD patients: a post hoc analysis of a randomized controlled trial.

BACKGROUND: Several randomized clinical trials have shown that non-invasive ventilation (NIV) applied immediately after extubation may prevent reintubation in patients at high-risk of extubation failure. However, most of studies included patients with chronic respiratory disorders as well as patients without underlying respiratory disease. To date, no study has shown decreased risk of reintubation with prophylactic NIV after extubation among patients with chronic obstructive pulmonary disease (COPD). We hypothesized that prophylactic NIV after extubation may decrease the risk of reintubation in COPD patients as compared with high-flow nasal oxygen. We performed a post hoc subgroup analysis of COPD patients included in a multicenter, randomized, controlled trial comparing prophylactic use of NIV alternating with high-flow nasal oxygen versus high-flow nasal oxygen alone immediately after extubation. RESULTS: Among the 651 patients included in the original study, 150 (23%) had underlying COPD including 86 patients treated with NIV alternating with high-flow nasal oxygen and 64 patients treated with high-flow nasal oxygen alone. The reintubation rate was 13% (11 out of 86 patients) with NIV and 27% (17 out of 64 patients) with high-flow nasal oxygen alone [difference, - 14% (95% CI - 27% to - 1%); p = 0.03]. Whereas reintubation rates were significantly lower with NIV than with high-flow nasal oxygen alone at 72 h and until ICU discharge, mortality in ICU did not differ between groups: 6% (5/86) with NIV vs. 9% (6/64) with high-flow nasal oxygen alone [difference - 4% (95% CI - 14% to 5%); p = 0.40]. CONCLUSIONS: In COPD patients, prophylactic NIV alternating with high-flow nasal oxygen significantly decreased the risk of reintubation compared with high-flow nasal oxygen alone. Trial registration The study was registered at http://www.clinicaltrials.gov with the trial registration number NCT03121482 (20 April 2017).

Prior Exposure to Angiotensin II Receptor Blockers in Patients With Septic Shock to Individualize Mean Arterial Pressure Target? A Post Hoc Analysis of the Sepsis and Mean Arterial Pressure (SEPSISPAM) Trial.

OBJECTIVES: Individualizing a target mean arterial pressure is challenging during the initial resuscitation of patients with septic shock. The Sepsis and Mean Arterial Pressure (SEPSISPAM) trial suggested that targeting high mean arterial pressure might reduce the occurrence of acute kidney injury among those included patients with a past history of chronic hypertension. We investigated whether the class of antihypertensive medications used before the ICU stay in chronic hypertensive patients was associated with the severity of acute kidney injury occurring after inclusion, according to mean arterial pressure target. DESIGN: Post hoc analysis of the SEPSISPAM trial. SETTING: The primary outcome was the occurrence of severe acute kidney injury during the ICU stay defined as kidney disease improving global outcome stage 2 or higher. Secondary outcomes were mortality at day 28 and mortality at day 90. PATIENTS: All patients with chronic hypertension included in SEPSISPAM with available antihypertensive medications data in the hospitalization report were included. MEASUREMENTS AND MAIN RESULTS: We analyzed 297 patients. Severe acute kidney injury occurred in 184 patients, without difference according to pre-ICU exposure to antihypertensive medications. Patients with pre-ICU exposure to angiotensin II receptor blockers had significantly less severe acute kidney injury in the high mean arterial pressure target group (adjusted odd ratio 0.24 with 95% CI [0.09-0.66]; p = 0.006). No statistically significant association was found after adjustment for pre-ICU exposure to antihypertensive medications and survival. CONCLUSIONS: Our results suggest that patients with septic shock and chronic hypertension treated with angiotensin II receptor blocker may benefit from a high mean arterial pressure target to reduce the risk of acute kidney injury occurrence.

Determinants of hospital and one-year mortality among older patients admitted to intensive care units: results from the multicentric SENIOREA cohort.

BACKGROUND: Improving outcomes of older patients admitted into intensive care units (ICU) is a raising concern. This study aimed at determining which geriatric and ICU parameters were associated with in-hospital and long-term mortality in this population. METHODS: We conducted a prospective multicentric observational cohort study, including patients aged 75 years and older requiring mechanical ventilation, admitted between September 2012 and December 2013 into ICU of 13 French hospitals. Comprehensive geriatric assessment at ICU admission and ICU usual parameters were registered in a standardized manner. Survival was recorded and comprehensive geriatric assessment was updated after 1 year during a dedicated home visit. RESULTS: 501 patients were analyzed. 108 patients (21.6%) died during the hospital stay. One-year survival rate was 53.8% (IC 95% [49.2%; 58.2%]). Factors associated with increased in-hospital mortality were higher acute illness severity score, resuscitated cardiac arrest as primary ICU diagnosis, perception of anxiety and low quality of life by the proxy, and living in a chronic care facility before ICU admission. Among patients alive at hospital discharge, factors associated with increased 1-year mortality in multivariate analysis were longer duration of mechanical ventilation, all primary ICU diagnoses other than septic shock, a Katz-activities of daily living (ADL) score below 5 and living in a chronic care facility before ICU admission. Among the 163 survivors at 1 year who received a second comprehensive geriatric assessment, the ADL score (functional abilities) showed a significant but moderate decline over time, whereas the Mini-Zarit score (family burden) improved. No significant change in patients' place of life was observed after 1 year, and quality of life was reported as happy-to-very-happy in 88% of survivors. CONCLUSIONS: The mortality rate remains high among older ICU patients requiring mechanical ventilation. Factors associated with short- and long-term mortality combined geriatric and ICU criteria, which should be jointly evaluated in routine care. Clinical trial registration NCT01679171.

Comparison of high-flow nasal oxygen therapy and non-invasive ventilation in ICU patients with acute respiratory failure and a do-not-intubate orders: a multicentre prospective study OXYPAL.

INTRODUCTION: A palliative approach to intensive care unit (ICU) patients with acute respiratory failure and a do-not-intubate order corresponds to a poorly evaluated target for non-invasive oxygenation treatments. Survival alone should not be the only target; it also matters to avoid discomfort and to restore the patient's quality of life. We aim to conduct a prospective multicentre observational study to analyse clinical practices and their impact on outcomes of palliative high-flow nasal oxygen therapy (HFOT) and non-invasive ventilation (NIV) in ICU patients with do-not-intubate orders. METHODS AND ANALYSIS: This is an investigator-initiated, multicentre prospective observational cohort study comparing the three following strategies of oxygenation: HFOT alone, NIV alternating with HFOT and NIV alternating with standard oxygen in patients admitted in the ICU for acute respiratory failure with a do-not-intubate order. The primary outcome is the hospital survival within 14 days after ICU admission in patients weaned from NIV and HFOT. The sample size was estimated at a minimum of 330 patients divided into three groups according to the oxygenation strategy applied. The analysis takes into account confounding factors by modelling a propensity score. 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: NCT03673631.

Predictors of hospital discharge and mortality in patients with diabetes and COVID-19: updated results from the nationwide CORONADO study.

AIMS/HYPOTHESIS: This is an update of the results from the previous report of the CORONADO (Coronavirus SARS-CoV-2 and Diabetes Outcomes) study, which aims to describe the outcomes and prognostic factors in patients with diabetes hospitalised for coronavirus disease-2019 (COVID-19). METHODS: The CORONADO initiative is a French nationwide multicentre study of patients with diabetes hospitalised for COVID-19 with a 28-day follow-up. The patients were screened after hospital admission from 10 March to 10 April 2020. We mainly focused on hospital discharge and death within 28 days. RESULTS: We included 2796 participants: 63.7% men, mean age 69.7 ± 13.2 years, median BMI (25th-75th percentile) 28.4 (25.0-32.4) kg/m2. Microvascular and macrovascular diabetic complications were found in 44.2% and 38.6% of participants, respectively. Within 28 days, 1404 (50.2%; 95% CI 48.3%, 52.1%) were discharged from hospital with a median duration of hospital stay of 9 (5-14) days, while 577 participants died (20.6%; 95% CI 19.2%, 22.2%). In multivariable models, younger age, routine metformin therapy and longer symptom duration on admission were positively associated with discharge. History of microvascular complications, anticoagulant routine therapy, dyspnoea on admission, and higher aspartate aminotransferase, white cell count and C-reactive protein levels were associated with a reduced chance of discharge. Factors associated with death within 28 days mirrored those associated with discharge, and also included routine treatment by insulin and statin as deleterious factors. CONCLUSIONS/INTERPRETATION: In patients with diabetes hospitalised for COVID-19, we established prognostic factors for hospital discharge and death that could help clinicians in this pandemic period. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT04324736.