Inhaled Amikacin to Prevent Ventilator-Associated Pneumonia.

BACKGROUND: Whether preventive inhaled antibiotics may reduce the incidence of ventilator-associated pneumonia is unclear. METHODS: In this investigator-initiated, multicenter, double-blind, randomized, controlled, superiority trial, we assigned critically ill adults who had been undergoing invasive mechanical ventilation for at least 72 hours to receive inhaled amikacin at a dose of 20 mg per kilogram of ideal body weight once daily or to receive placebo for 3 days. The primary outcome was a first episode of ventilator-associated pneumonia during 28 days of follow-up. Safety was assessed. RESULTS: A total of 850 patients underwent randomization, and 847 were included in the analyses (417 assigned to the amikacin group and 430 to the placebo group). All three daily nebulizations were received by 337 patients (81%) in the amikacin group and 355 patients (83%) in the placebo group. At 28 days, ventilator-associated pneumonia had developed in 62 patients (15%) in the amikacin group and in 95 patients (22%) in the placebo group (difference in restricted mean survival time to ventilator-associated pneumonia, 1.5 days; 95% confidence interval [CI], 0.6 to 2.5; P = 0.004). An infection-related ventilator-associated complication occurred in 74 patients (18%) in the amikacin group and in 111 patients (26%) in the placebo group (hazard ratio, 0.66; 95% CI, 0.50 to 0.89). Trial-related serious adverse effects were seen in 7 patients (1.7%) in the amikacin group and in 4 patients (0.9%) in the placebo group. CONCLUSIONS: Among patients who had undergone mechanical ventilation for at least 3 days, a subsequent 3-day course of inhaled amikacin reduced the burden of ventilator-associated pneumonia during 28 days of follow-up. (Funded by the French Ministry of Health; AMIKINHAL ClinicalTrials.gov number, NCT03149640; EUDRA Clinical Trials number, 2016-001054-17.).

Spontaneous-Breathing Trials with Pressure-Support Ventilation or a T-Piece.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.).

Place of high-flow nasal oxygen in nonoperating room anesthesia.

PURPOSE OF REVIEW: This article aims to assess the utility of high-flow nasal oxygen (HFNO) therapy in nonoperating room anesthesia (NORA) settings. RECENT FINDINGS: The number of procedural interventions under deep sedation in NORA is still increasing. Administration of oxygen is recommended to prevent hypoxemia and is usually delivered with standard oxygen through nasal cannula or a face mask. HFNO is a simple alternative with a high warmed humidified flow (ranging from 30 to 70 l/min) with a precise fraction inspired of oxygen (ranging from 21 to 100%). Compared to standard oxygen, HFNO has demonstrated efficacy in reducing the incidence of hypoxemia and the need for airway maneuvers. Research on HFNO has primarily focused on its application in gastrointestinal endoscopy procedures. Yet, it has also shown promising results in various other procedural interventions including bronchoscopy, cardiology, and endovascular procedures. However, the adoption of HFNO prompted considerations regarding cost-effectiveness and environmental impact. SUMMARY: HFNO emerges as a compelling alternative to conventional oxygen delivery methods for preventing hypoxemia during procedural interventions in NORA. However, its utilization should be reserved for patients at moderate-to-high risk to mitigate the impact of cost and environmental factors.

Noninvasive Monitoring of Arterial Pressure: Finger or Lower Leg As Alternatives to the Upper Arm: A Prospective Study in Three ICUs.

OBJECTIVES: When the upper arm is inaccessible for measurements of arterial pressure (AP), the best alternative site is unknown. We performed a between-site comparison of the agreement between invasive and noninvasive readings of AP taken at the lower leg, the finger, and the upper arm. The risk associated with measurement errors and the trending ability were also assessed. DESIGN: Prospective observational study. SETTING: Three ICUs. PATIENTS: Patients having an arterial catheter and an arm circumference less than 42 cm. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Three triplicates of AP measurements were collected via an arterial catheter (reference AP), a finger cuff system (ClearSight; Edward Lifesciences, Irvine, CA), and an oscillometric cuff (at the lower leg then the upper arm). Trending ability was assessed through an additional set of measurements after a cardiovascular intervention. The default bed backrest angle was respected. Failure to measure and display AP occurred in 19 patients (13%) at the finger, never at other sites. In 130 patients analyzed, the agreement between noninvasive and invasive readings was worse at the lower leg than that observed at the upper arm or the finger (for mean AP, bias ± sd of 6.0 ± 15.8 vs 3.6 ± 7.1 and 0.1 ± 7.4 mm Hg, respectively; p < 0.05), yielding a higher frequency of error-associated clinical risk (no risk for 64% vs 84% and 86% of measurements, respectively, p < 0.0001). According to the International Organization for Standardization (ISO) 81060-2:2018 standard, mean AP measurements were reliable at the upper arm and the finger, not the lower leg. In 33 patients reassessed after a cardiovascular intervention, both the concordance rate for change in mean AP and the ability to detect a therapy-induced significant change were good and similar at the three sites. CONCLUSIONS: As compared with lower leg measurements of AP, finger measurements were, when possible, a preferable alternative to upper arm ones.

Prone position versus usual care in hypoxemic COVID-19 patients in medical wards: a randomised controlled trial.

BACKGROUND: Benefit of early awake prone positioning for COVID-19 patients hospitalised in medical wards and who need oxygen therapy remains to be demonstrated. The question was considered at the time of COVID-19 pandemic to avoid overloading the intensive care units. We aimed to determine whether prone position plus usual care could reduce the rate of non-invasive ventilation (NIV) or intubation or death as compared to usual care alone. METHODS: In this multicentre randomised clinical trial, 268 patients were randomly assigned to awake prone position plus usual care (N = 135) or usual care alone (N = 132). The primary outcome was the proportion of patients who underwent NIV or intubation or died within 28 days. Main secondary outcomes included the rates of NIV, of intubation or death, within 28 days. RESULTS: Median time spent each day in the prone position within 72 h of randomisation was 90 min (IQR 30-133). The proportion of NIV or intubation or death within 28 days was 14.1% (19/135) in the prone position group and 12.9% (17/132) in the usual care group [odds ratio adjusted for stratification (aOR) 0.43; 95% confidence interval (CI) 0.14-1.35]. The probability of intubation, or intubation or death (secondary outcomes) was lower in the prone position group than in the usual care group (aOR 0.11; 95% CI 0.01-0.89 and aOR 0.09; 95% CI 0.01-0.76, respectively) in the whole study population and in the prespecified subgroup of patients with SpO2 ≥ 95% on inclusion (aOR 0.11; 95% CI 0.01-0.90, and aOR 0.09; 95% CI 0.03-0.27, respectively). CONCLUSIONS: Awake prone position plus usual care in COVID-19 patients in medical wards did not decrease the composite outcome of need for NIV or intubation or death. Trial registration ClinicalTrials.gov Identifier: NCT04363463 . Registered 27 April 2020.

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).

Relying on pulse oximetry to avoid hypoxaemia and hyperoxia: A multicentre prospective cohort study in patients with circulatory failure.

PURPOSE: The purpose of this study was to assess the predictive performance of pulse oximetry (SpO2) to rule out hypoxaemia and hyperoxia in critically ill patients. METHODS: SpO2, arterial oxygenation (SaO2), and arterial partial pressure of oxygen (PaO2) were prospectively and simultaneously measured every 6 h during the first 24 h of intensive care unit admission in a multicentre cohort of critically ill patients suffering acute circulatory failure. Likelihood ratios associated with different cutoff values of SpO2 to rule out hypoxaemia (SaO2 < 90% or PaO2 < 60 mmHg) or hyperoxia (SaO2 > 95% or PaO2 > 100 mmHg) and post-test probabilities were calculated. Mean bias between SpO2 and SaO2 and agreement interval were calculated. Area under the receiver operating characteristics associated with SpO2 to predict different threshold values of SaO2 and PaO2 were calculated. RESULTS: Five hundred seventy-one patients (mean [standard deviation] Simplified Acute Physiology Score II: 58.7 [20.1]; mechanically ventilated 75.6%) with 2643 available SaO2 and PaO2 samples and corresponding 2643 SpO2 values were analysed. Mean bias between SpO2 and SaO2 was 1.1%, and its agreement interval ranged from -8.2 to +11.1%. SpO2 cutoff values of 88%, 90%, and 92% left the possibility that 8%-13% of patients had hypoxaemia. SpO2 < 95% left the possibility that 31% of patients had hyperoxia. All calculated areas under the receiver operating characteristics showed a lower limit of their 95% confidence interval below 0.85 CONCLUSION: In this cohort of patients with circulatory failure, SpO2 had poor discriminative ability to rule out hypoxaemia and hyperoxia. Overconfidence upon SpO2 monitoring may be dangerous.

Effect of a Musical Intervention During the Implantation of a Central Venous Catheter or a Dialysis Catheter in the Intensive Care Unit: A Prospective Randomized Pilot Study.

BACKGROUND: Listening to music may reduce anxiety during medical procedures. However, the magnitude of any effect may differ with respect to patient and procedure. We evaluated the effect of a musical intervention on patient anxiety during a central venous catheter or dialysis catheter implantation in an intensive care unit. METHODS: A prospective single-center controlled open-label 2-arm randomized trial was conducted in a medical intensive care unit (ICU) from February 2018 to February 2019. Patients undergoing central venous catheterization were randomized to listening to music or not during the procedure. Patients randomized to music listened to the Music Care application via headphones. The primary outcome was the change in anxiety assessed on a 100-mm Visual Analogue Scale between the beginning and end of the catheterization procedure. Secondary outcomes included postprocedural pain. RESULTS: We included 37 patients in the musical intervention group and 35 in the standard care group. The primary reasons for intensive care unit admission were the need for a central catheter for chemotherapy for hematologic malignancy and sepsis and/or septic shock in both groups. Postprocedural anxiety and pain assessments were missing in 1 (2.7%) and 4 (11.4%) patients in the intervention and standard care groups. We found no between-group difference in change in anxiety score: median -1 (interquartile range, -3 to 0) vs 0 (-3 to 0) in the musical intervention and standard care groups (median difference, -1 [-2 to 0]) (P = .24). Postprocedural pain score did not differ between the groups: median 0 (0-2) and 0 (0-3.75) in the musical intervention and standard care groups (median difference, -0 [0-0]) (P = .40). To account for missing outcome assessments, sensitivity analyses were performed using 2 extreme scenarios, one favoring the standard care group (scenario 1) and the other favoring the intervention group (scenario 2). In either scenario, change in anxiety score did not differ between the intervention and standard care groups: -1 (-3 to 0) vs 0 (-4 to 0) (P = .88) in scenario 1 and -1 (-3 to 0) vs 0 (-2.75 to 1) (P = .07) in scenario 2. CONCLUSIONS: In this first randomized pilot study of musical intervention for central venous catheterization in awake patients in the intensive care unit, the musical intervention did not reduce patients' anxiety as compared with usual care.

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.

Timing of Renal-Replacement Therapy in Patients with Acute Kidney Injury and Sepsis.

BACKGROUND: Acute kidney injury is the most frequent complication in patients with septic shock and is an independent risk factor for death. Although renal-replacement therapy is the standard of care for severe acute kidney injury, the ideal time for initiation remains controversial. METHODS: In a multicenter, randomized, controlled trial, we assigned patients with early-stage septic shock who had severe acute kidney injury at the failure stage of the risk, injury, failure, loss, and end-stage kidney disease (RIFLE) classification system but without life-threatening complications related to acute kidney injury to receive renal-replacement therapy either within 12 hours after documentation of failure-stage acute kidney injury (early strategy) or after a delay of 48 hours if renal recovery had not occurred (delayed strategy). The failure stage of the RIFLE classification system is characterized by a serum creatinine level 3 times the baseline level (or ≥4 mg per deciliter with a rapid increase of ≥0.5 mg per deciliter), urine output less than 0.3 ml per kilogram of body weight per hour for 24 hours or longer, or anuria for at least 12 hours. The primary outcome was death at 90 days. RESULTS: The trial was stopped early for futility after the second planned interim analysis. A total of 488 patients underwent randomization; there were no significant between-group differences in the characteristics at baseline. Among the 477 patients for whom follow-up data at 90 days were available, 58% of the patients in the early-strategy group (138 of 239 patients) and 54% in the delayed-strategy group (128 of 238 patients) had died (P=0.38). In the delayed-strategy group, 38% (93 patients) did not receive renal-replacement therapy. Criteria for emergency renal-replacement therapy were met in 17% of the patients in the delayed-strategy group (41 patients). CONCLUSIONS: Among patients with septic shock who had severe acute kidney injury, there was no significant difference in overall mortality at 90 days between patients who were assigned to an early strategy for the initiation of renal-replacement therapy and those who were assigned to a delayed strategy. (Funded by the French Ministry of Health; IDEAL-ICU ClinicalTrials.gov number, NCT01682590 .).

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.

High-flow nasal oxygenation or standard oxygenation for gastrointestinal endoscopy with sedation in patients at risk of hypoxaemia: a multicentre randomised controlled trial (ODEPHI trial).

BACKGROUND: We aimed to determine whether high-flow nasal oxygen could reduce the incidence of decreased peripheral oxygen saturation (SpO2) compared with standard oxygen in patients at risk of hypoxaemia undergoing gastrointestinal endoscopy under deep sedation. METHODS: This was a multicentre, randomised controlled trial with blinded assessment of the primary outcome evaluating high-flow nasal oxygen (gas flow 70 L min-1, inspired oxygen fraction 0.50) or standard oxygen delivered via nasal cannula or face mask (6 L min-1) or nasopharyngeal tube (5 L min-1) in patients at risk of hypoxaemia (i.e. >60 yr old, or with underlying cardiac or respiratory disease, or with ASA physical status >1, or with obesity or sleep apnoea syndrome) undergoing gastrointestinal endoscopy. The primary endpoint was the incidence of SpO2 ≤92%. Secondary outcomes included prolonged or severe desaturations, need for manoeuvres to maintain free upper airways, and other adverse events. RESULTS: In 379 patients, a decrease in SpO2 ≤92% occurred in 9.4% (18/191) for the high-flow nasal oxygen group, and 33.5% (63/188) for the standard oxygen groups (adjusted absolute risk difference, -23.4% [95% confidence interval (CI), -28.9 to -16.7]; P<0.001). Prolonged desaturation (>1 min) and manoeuvres to maintain free upper airways were less frequent in the high-flow nasal oxygen group than in the standard oxygen group (7.3% vs 14.9%, P=.02, and 11.1% vs 32.4%, P<0.001). CONCLUSIONS: In patients at risk of hypoxaemia undergoing gastrointestinal endoscopy under deep sedation, use of high-flow nasal oxygen significantly reduced the incidence of peripheral oxygen desaturation. CLINICAL TRIAL REGISTRATION: NCT03829293.

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.

Effect of In-Bed Leg Cycling and Electrical Stimulation of the Quadriceps on Global Muscle Strength in Critically Ill Adults: A Randomized Clinical Trial.

Importance: Early in-bed cycling and electrical muscle stimulation may improve the benefits of rehabilitation in patients in the intensive care unit (ICU). Objective: To investigate whether early in-bed leg cycling plus electrical stimulation of the quadriceps muscles added to standardized early rehabilitation would result in greater muscle strength at discharge from the ICU. Design, Setting, and Participants: Single-center, randomized clinical trial enrolling critically ill adult patients at 1 ICU within an 1100-bed hospital in France. Enrollment lasted from July 2014 to June 2016 and there was a 6-month follow-up, which ended on November 24, 2016. Interventions: Patients were randomized to early in-bed leg cycling plus electrical stimulation of the quadriceps muscles added to standardized early rehabilitation (n = 159) or standardized early rehabilitation alone (usual care) (n = 155). Main Outcomes and Measures: The primary outcome was muscle strength at discharge from the ICU assessed by physiotherapists blinded to treatment group using the Medical Research Council grading system (score range, 0-60 points; a higher score reflects better muscle strength; minimal clinically important difference of 4 points). Secondary outcomes at ICU discharge included the number of ventilator-free days and ICU Mobility Scale score (range, 0-10; a higher score reflects better walking capability). Functional autonomy and health-related quality of life were assessed at 6 months. Results: Among 314 randomized patients, 312 (mean age, 66 years; women, 36%; receiving mechanical ventilation at study inclusion, 78%) completed the study and were included in the analysis. The median global Medical Research Council score at ICU discharge was 48 (interquartile range [IQR], 29 to 58) in the intervention group and 51 (IQR, 37 to 58) in the usual care group (median difference, -3.0 [95% CI, -7.0 to 2.8]; P = .28). The ICU Mobility Scale score at ICU discharge was 6 (IQR, 3 to 9) in both groups (median difference, 0 [95% CI, -1 to 2]; P = .52). The median number of ventilator-free days at day 28 was 21 (IQR, 6 to 25) in the intervention group and 22 (IQR, 10 to 25) in the usual care group (median difference, 1 [95% CI, -2 to 3]; P = .24). Clinically significant events occurred during mobilization sessions in 7 patients (4.4%) in the intervention group and in 9 patients (5.8%) in the usual care group. There were no significant between-group differences in the outcomes assessed at 6 months. Conclusions and Relevance: In this single-center randomized clinical trial involving patients admitted to the ICU, adding early in-bed leg cycling exercises and electrical stimulation of the quadriceps muscles to a standardized early rehabilitation program did not improve global muscle strength at discharge from the ICU. Trial Registration: ClinicalTrials.gov Identifier: NCT02185989.

Risk factors for poor performance in finger cuff non-invasive monitoring of arterial pressure: A prospective multicenter study.

BACKGROUND: Compared to the invasive technique, non-invasive monitoring of arterial pressure favors easier and faster implementation while potentially sacrificing some reliability. This may be particularly true for the Clearsight™ system (Edwards Lifesciences), which enables continuous monitoring. We evaluated the risk factors for its poor performance. METHODS: Patients with an arterial catheter and stable mean arterial pressure (MAP) over a 5-min period were included. Six pairs of invasive and Clearsight measurements of MAP were collected and the bias between the two techniques was calculated. Poor performance of the Clearsight™ system was defined as either a failure to measure and display MAP or displaying an erroneous MAP (individual bias > 5 mmHg). Fingertip perfusion was assessed using the plethysmographic perfusion index (PI) and the capillary refill time (CRT). RESULTS: Among 152 ICU patients (MAP of 81 ± 14 mmHg, norepinephrine in 78 [51%]), 78 (51%) experienced a poor performance of the Clearsight™ system: failure to display MAP in 19 (13%) patients, and erroneous value displayed in 59 (44%). In multivariate analysis, PI ≤ 0.85% (adjusted odds ratio [aOR] = 2.94 [95% confidence interval (95%CI):1.34;6.45]), CRT > 4 s (aOR = 5.28 [95%CI 1.39;20.05]), and the presence of hand edema (aOR = 2.06 [95%CI 1.01;4.21]) were associated with a higher likelihood of poor performance. Cardiac arrhythmia (aOR = 1.39 [95%CI 0.64;3.02]) and other tested variables were not associated with poor performance. CONCLUSIONS: Half of the included patients exhibited poor Clearsight™ system performance. Our results caution against using finger cuff arterial pressure monitoring in patients with low PI (≤0.85%), protracted CRT (>4 s), or hand edema. REGISTRATION: ClinicalTrials.gov, NCT04269382, Dr. G. Muller, February 13, 2020. https://classic. CLINICALTRIALS: gov/ct2/show/NCT04269382.

Continued enteral nutrition until extubation compared with fasting before extubation in patients in the intensive care unit: an open-label, cluster-randomised, parallel-group, non-inferiority trial.

BACKGROUND: Fasting is frequently imposed before extubation in patients in intensive care units, with the aim to reduce risk of aspiration. This unevaluated practice might delay extubation, increase workload, and reduce caloric intake. We aimed to compare continued enteral nutrition until extubation with fasting before extubation in patients in the intensive care unit. METHODS: We conducted an open-label, cluster-randomised, parallel-group, non-inferiority trial in 22 intensive care units in France. Patients aged 18 years or older were eligible for enrolment if they had received invasive mechanical ventilation for at least 48 h in the intensive care unit and received prepyloric enteral nutrition for at least 24 h at the time of extubation decision. Centres were randomly assigned (1:1) to continued enteral nutrition until extubation or 6-h fasting with concomitant gastric suctioning before extubation, to be applied for all patients within the unit. Masking was not possible because of the nature of the trial. The primary outcome was extubation failure (composite criteria of reintubation or death) within 7 days after extubation, assessed in both the intention-to-treat and per-protocol populations. The non-inferiority margin was set at 10%. Pneumonia within 14 days of extubation was a key secondary endpoint. This trial is now complete and is registered with ClinicalTrials.gov, NCT03335345. FINDINGS: Between April 1, 2018, and Oct 31, 2019, 7056 patients receiving enteral nutrition and mechanical ventilation were admitted to the intensive care units and 4198 were assessed for eligibility. 1130 patients were enrolled and included in the intention-to-treat population and 1008 were included in the per-protocol population. In the intention-to-treat population, extubation failure occurred in 106 (17·2%) of 617 patients assigned to receive continued enteral nutrition until extubation versus 90 (17·5%) of 513 assigned to fasting, meeting the a priori defined non-inferiority criterion (absolute difference -0·4%, 95% CI -5·2 to 4·5). In the per-protocol population, extubation failure occurred in 101 (17·0%) of 595 patients assigned to receive continued enteral nutrition versus 74 (17·9%) of 413 assigned to fasting (absolute difference -0·9%, 95% CI -5·6 to 3·7). Pneumonia within 14 days of extubation occurred in ten (1·6%) patients assigned to receive continued enteral nutrition and 13 (2·5%) assigned to fasting (rate ratio 0·77, 95% CI 0·22 to 2·69). INTERPRETATION: Continued enteral nutrition until extubation in critically ill patients in the intensive care unit was non-inferior to a 6-h fasting maximum gastric vacuity strategy comprising continuous gastric tube suctioning, in terms of extubation failure within 7 days (a patient-centred outcome), and thus represents a potential alternative in this population. FUNDING: French Ministry of Health. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Low versus standard calorie and protein feeding in ventilated adults with shock: a randomised, controlled, multicentre, open-label, parallel-group trial (NUTRIREA-3).

BACKGROUND: The optimal calorie and protein intakes at the acute phase of severe critical illness remain unknown. We hypothesised that early calorie and protein restriction improved outcomes in these patients, compared with standard calorie and protein targets. METHODS: The pragmatic, randomised, controlled, multicentre, open-label, parallel-group NUTRIREA-3 trial was performed in 61 French intensive care units (ICUs). Adults (≥18 years) receiving invasive mechanical ventilation and vasopressor support for shock were randomly assigned to early nutrition (started within 24 h after intubation) with either low or standard calorie and protein targets (6 kcal/kg per day and 0·2-0·4 g/kg per day protein vs 25 kcal/kg per day and 1·0-1·3 g/kg per day protein) during the first 7 ICU days. The two primary endpoints were time to readiness for ICU discharge and day 90 all-cause mortality. Key secondary outcomes included secondary infections, gastrointestinal events, and liver dysfunction. The trial is registered on ClinicalTrials.gov, NCT03573739, and is completed. FINDINGS: Of 3044 patients randomly assigned between July 5, 2018, and 8 Dec 8, 2020, eight withdrew consent to participation. By day 90, 628 (41·3%) of 1521 patients in the low group and 648 (42·8%) of 1515 patients in the standard group had died (absolute difference -1·5%, 95% CI -5·0 to 2·0; p=0·41). Median time to readiness for ICU discharge was 8·0 days (IQR 5·0-14·0) in the low group and 9·0 days (5·0-17·0) in the standard group (hazard ratio [HR] 1·12, 95% CI 1·02 to 1·22; p=0·015). Proportions of patients with secondary infections did not differ between the groups (HR 0·85, 0·71 to 1·01; p=0·06). The low group had lower proportions of patients with vomiting (HR 0·77, 0·67 to 0·89; p<0·001), diarrhoea (0·83, 0·73 to 0·94; p=0·004), bowel ischaemia (0·50, 0·26 to 0·95; p=0·030), and liver dysfunction (0·92, 0·86-0·99; p=0·032). INTERPRETATION: Compared with standard calorie and protein targets, early calorie and protein restriction did not decrease mortality but was associated with faster recovery and fewer complications. FUNDING: French Ministry of Health.

Does awake prone positioning prevent the use of mechanical respiratory support or death in COVID-19 patients on standard oxygen therapy hospitalised in general wards? A multicentre randomised controlled trial: the PROVID-19 protocol.

INTRODUCTION: COVID-19 is responsible of severe hypoxaemia and acute respiratory distress syndrome (ARDS). Prone positioning improves oxygenation and survival in sedated mechanically patients with ARDS not related to COVID-19. Awake prone positioning is a simple and safe technique which improves oxygenation in non-intubated COVID-19 patients. We hypothesised that early prone positioning in COVID-19 patients breathing spontaneously in medical wards could decrease the rates of intubation or need for noninvasive ventilation or death. METHODS AND ANALYSIS: PROVID-19 is an investigator-initiated, prospective, multicentre randomised, controlled, superiority trial comparing awake prone positioning to standard of care in hypoxaemic COVID-19 patients in 20 medical wards in France and Monaco. Patients are randomised to receive either awake prone position plus usual care or usual care alone with stratification on centres, body mass index and severity of hypoxaemia.The study objective is to compare the rate of treatment failure defined as a composite endpoint comprising the need for non-invasive ventilation (at two pressure levels) or for intubation or death, between the intervention group (awake prone position plus usual care) and the usual care (usual care alone) group at 28 days. ETHICS AND DISSEMINATION: The protocol and amendments have been approved by the ethics committees (Comité de protection des personnes Ouest VI, France, no 1279 HPS2 and Comité Consultatif d'Ethique en matière de Recherche Biomédicale, Monaco, no 2020.8894 AP/jv), and patients are included after written informed consent. The results will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04363463.