Hydrocortisone in Severe Community-Acquired Pneumonia.

BACKGROUND: Whether the antiinflammatory and immunomodulatory effects of glucocorticoids may decrease mortality among patients with severe community-acquired pneumonia is unclear. METHODS: In this phase 3, multicenter, double-blind, randomized, controlled trial, we assigned adults who had been admitted to the intensive care unit (ICU) for severe community-acquired pneumonia to receive intravenous hydrocortisone (200 mg daily for either 4 or 7 days as determined by clinical improvement, followed by tapering for a total of 8 or 14 days) or to receive placebo. All the patients received standard therapy, including antibiotics and supportive care. The primary outcome was death at 28 days. RESULTS: A total of 800 patients had undergone randomization when the trial was stopped after the second planned interim analysis. Data from 795 patients were analyzed. By day 28, death had occurred in 25 of 400 patients (6.2%; 95% confidence interval [CI], 3.9 to 8.6) in the hydrocortisone group and in 47 of 395 patients (11.9%; 95% CI, 8.7 to 15.1) in the placebo group (absolute difference, -5.6 percentage points; 95% CI, -9.6 to -1.7; P = 0.006). Among the patients who were not undergoing mechanical ventilation at baseline, endotracheal intubation was performed in 40 of 222 (18.0%) in the hydrocortisone group and in 65 of 220 (29.5%) in the placebo group (hazard ratio, 0.59; 95% CI, 0.40 to 0.86). Among the patients who were not receiving vasopressors at baseline, such therapy was initiated by day 28 in 55 of 359 (15.3%) of the hydrocortisone group and in 86 of 344 (25.0%) in the placebo group (hazard ratio, 0.59; 95% CI, 0.43 to 0.82). The frequencies of hospital-acquired infections and gastrointestinal bleeding were similar in the two groups; patients in the hydrocortisone group received higher daily doses of insulin during the first week of treatment. CONCLUSIONS: Among patients with severe community-acquired pneumonia being treated in the ICU, those who received hydrocortisone had a lower risk of death by day 28 than those who received placebo. (Funded by the French Ministry of Health; CAPE COD ClinicalTrials.gov number, NCT02517489.).

Compassionate Use of Remdesivir for Patients with Severe Covid-19.

BACKGROUND: Remdesivir, a nucleotide analogue prodrug that inhibits viral RNA polymerases, has shown in vitro activity against SARS-CoV-2. METHODS: We provided remdesivir on a compassionate-use basis to patients hospitalized with Covid-19, the illness caused by infection with SARS-CoV-2. Patients were those with confirmed SARS-CoV-2 infection who had an oxygen saturation of 94% or less while they were breathing ambient air or who were receiving oxygen support. Patients received a 10-day course of remdesivir, consisting of 200 mg administered intravenously on day 1, followed by 100 mg daily for the remaining 9 days of treatment. This report is based on data from patients who received remdesivir during the period from January 25, 2020, through March 7, 2020, and have clinical data for at least 1 subsequent day. RESULTS: Of the 61 patients who received at least one dose of remdesivir, data from 8 could not be analyzed (including 7 patients with no post-treatment data and 1 with a dosing error). Of the 53 patients whose data were analyzed, 22 were in the United States, 22 in Europe or Canada, and 9 in Japan. At baseline, 30 patients (57%) were receiving mechanical ventilation and 4 (8%) were receiving extracorporeal membrane oxygenation. During a median follow-up of 18 days, 36 patients (68%) had an improvement in oxygen-support class, including 17 of 30 patients (57%) receiving mechanical ventilation who were extubated. A total of 25 patients (47%) were discharged, and 7 patients (13%) died; mortality was 18% (6 of 34) among patients receiving invasive ventilation and 5% (1 of 19) among those not receiving invasive ventilation. CONCLUSIONS: In this cohort of patients hospitalized for severe Covid-19 who were treated with compassionate-use remdesivir, clinical improvement was observed in 36 of 53 patients (68%). Measurement of efficacy will require ongoing randomized, placebo-controlled trials of remdesivir therapy. (Funded by Gilead Sciences.).

Elevations of Extracellular Vesicles and Inflammatory Biomarkers in Closed Circuit SCUBA Divers.

Blood-borne extracellular vesicles and inflammatory mediators were evaluated in divers using a closed circuit rebreathing apparatus and custom-mixed gases to diminish some diving risks. "Deep" divers (n = 8) dove once to mean (±SD) 102.5 ± 1.2 m of sea water (msw) for 167.3 ± 11.5 min. "Shallow" divers (n = 6) dove 3 times on day 1, and then repetitively over 7 days to 16.4 ± 3.7 msw, for 49.9 ± 11.9 min. There were statistically significant elevations of microparticles (MPs) in deep divers (day 1) and shallow divers at day 7 that expressed proteins specific to microglia, neutrophils, platelets, and endothelial cells, as well as thrombospondin (TSP)-1 and filamentous (F-) actin. Intra-MP IL-1ß increased by 7.5-fold (p < 0.001) after day 1 and 41-fold (p = 0.003) at day 7. Intra-MP nitric oxide synthase-2 (NOS2) increased 17-fold (p < 0.001) after day 1 and 19-fold (p = 0.002) at day 7. Plasma gelsolin (pGSN) levels decreased by 73% (p < 0.001) in deep divers (day 1) and 37% in shallow divers by day 7. Plasma samples containing exosomes and other lipophilic particles increased from 186% to 490% among the divers but contained no IL-1ß or NOS2. We conclude that diving triggers inflammatory events, even when controlling for hyperoxia, and many are not proportional to the depth of diving.

Noninvasive Tidal Volume Measurements, Using a Time-of-Flight Camera, Under High-Flow Nasal Cannula-A Physiological Evaluation, in Healthy Volunteers.

OBJECTIVES: The mechanisms of high-flow nasal cannula are still debated but may be mediated by the generation of low positive end-expiratory pressure and a washout of the airway dead space. The aims of this study were to assess the effects of high-flow nasal cannula on tidal volume using a noninvasive method using a time-of-flight camera, under various conditions. DESIGN: A physiologic evaluation in healthy volunteers. SETTING: An university hospital ICU. SUBJECTS: Ten healthy volunteers were included in a physiologic study (CamOpt study, ClinicalTrials.gov identifier: NCT04096183). INTERVENTIONS: All volunteers were submitted to 12 different conditions (i.e., gas flow [baseline = 0; 30-60 L/min]; mouth [open/closed]; respiratory rate [baseline; baseline + 10 breaths/min]). Tidal volume measurements were performed every minute, during a 6-minute recording period. In all combinations, reference respiratory rate was measured by using chronometric evaluation, over a 30-second period (RRREF), and by using the time-of-flight camera (RRTOF). MEASUREMENTS AND MAIN RESULTS: Tidal volume increased while increasing gas flow whatever the respiratory rate and mouth condition (p < 0.001). Similar results were observed whatever the experimental conditions (p < 0.01), except one (baseline respiratory rate + 10 breaths/min and mouth closed). Tidal volume increased while decreasing respiratory rate (p < 0.001) and mouth closing (p < 0.05). Proportion of tidal volume greater than 10, 15, and 20 mL/kg changed while increasing the flow. RRTOF was in agreement with RRREF (intraclass correlation coefficient, 0.96), with a low mean bias (0.55 breaths/min) and acceptable deviation. CONCLUSIONS: Time-of-flight enables to detect tidal volume changes under various conditions of high-flow nasal cannula application. Tidal volume increased significantly while increasing gas flow and mouth closing. Such technique might be useful to monitor the risk of patient self-inflicted lung injury or under assistance.

Accuracy of noncontact surface imaging for tidal volume and respiratory rate measurements in the ICU.

Tidal volume monitoring may help minimize lung injury during respiratory assistance. Surface imaging using time-of-flight camera is a new, non-invasive, non-contact, radiation-free, and easy-to-use technique that enables tidal volume and respiratory rate measurements. The objectives of the study were to determine the accuracy of Time-of-Flight volume (VTTOF) and respiratory rate (RRTOF) measurements at the bedside, and to validate its application for spontaneously breathing patients under high flow nasal canula. Data analysis was performed within the ReaSTOC data-warehousing project (ClinicalTrials.gov identifier NCT02893462). All data were recorded using standard monitoring devices, and the computerized medical file. Time-of-flight technique used a Kinect V2 (Microsoft, Redmond, WA, USA) to acquire the distance information, based on measuring the phase delay between the emitted light-wave and received backscattered signals. 44 patients (32 under mechanical ventilation; 12 under high-flow nasal canula) were recorded. High correlation (r = 0.84; p < 0.001), with low bias (-1.7 mL) and acceptable deviation (75 mL) was observed between VTTOF and VTREF under ventilation. Similar performance was observed for respiratory rate (r = 0.91; p < 0.001; bias < 1b/min; deviation ≤ 5b/min). Measurements were possible for all patients under high-flow nasal canula, detecting overdistension in 4 patients (tidal volume > 8 mL/kg) and low ventilation in 6 patients (tidal volume < 6 mL/kg). Tidal volume monitoring using time-of-flight camera (VTTOF) is correlated to reference values. Time-of-flight camera enables continuous and non-contact respiratory monitoring under high-flow nasal canula, and enables to detect tidal volume and respiratory rate changes, while modifying flow. It enables respiratory monitoring for spontaneously patients, especially while using high-flow nasal oxygenation.

Pulmonary Effects of One Week of Repeated Recreational Closed-Circuit Rebreather Dives in Cold Water.

Background and Objectives: The use of closed-circuit rebreathers (CCRs) in recreational diving is gaining interest. However, data regarding its physiological effects are still scarce. Immersion, cold water, hyperoxia, exercise or the equipment itself could challenge the cardiopulmonary system. The purpose of this study was to examine the impact of CCR diving on lung function and autonomous cardiac activity after a series of CCR dives in cold water. Materials and Methods: Eight CCR divers performed a diving trip (one week) in the Baltic Sea. Spirometry parameters, SpO2, and the lung ultrasonography score (LUS) associated with hydration monitoring by bioelectrical impedance were assessed at the end of the week. Heart rate variability (HRV) was recorded during the dives. Results: No diver declared pulmonary symptoms. The LUS increased after dives combined with a slight non-pathological decrease in SpO2. Spirometry was not altered, and all body water compartments were increased. Global HRV decreased during diving with a predominant increase in sympathetic tone while the parasympathetic tone decreased. All parameters returned to baseline 24 h after the last dive. Conclusions: The lung aeration disorders observed seem to be transient and not associated with functional spirometry alteration. The HRV dynamics highlighted physiological constraints during the dive as well as environmental-stress-related stimulation that may influence pulmonary changes. The impact of these impairments is unknown but should be taken into account, especially when considering long and repetitive CCR dives.

Automated closed-loop versus standard manual oxygen administration after major abdominal or thoracic surgery: an international multicentre randomised controlled study.

INTRODUCTION: Hypoxaemia and hyperoxaemia may occur after surgery, with related complications. This multicentre randomised trial evaluated the impact of automated closed-loop oxygen administration after high-risk abdominal or thoracic surgeries in terms of optimising the oxygen saturation measured by pulse oximetry time within target range. METHODS: After extubation, patients with an intermediate to high risk of post-operative pulmonary complications were randomised to "standard" or "automated" closed-loop oxygen administration. The primary outcome was the percentage of time within the oxygenation range, during a 3-day frame. The secondary outcomes were the time with hypoxaemia and hyperoxaemia under oxygen. RESULTS: Among the 200 patients, time within range was higher in the automated group, both initially (≤3 h; 91.4±13.7% versus 40.2±35.1% of time, difference +51.0% (95% CI -42.8-59.2%); p<0.0001) and during the 3-day period (94.0±11.3% versus 62.1±23.3% of time, difference +31.9% (95% CI 26.3-37.4%); p<0.0001). Periods of hypoxaemia were reduced in the automated group (≤3 days; 32.6±57.8 min (1.2±1.9%) versus 370.5±594.3 min (5.0±11.2%), difference -10.2% (95% CI -13.9--6.6%); p<0.0001), as well as hyperoxaemia under oxygen (≤3 days; 5.1±10.9 min (4.8±11.2%) versus 177.9±277.2 min (27.0±23.8%), difference -22.0% (95% CI -27.6--16.4%); p<0.0001). Kaplan-Meier analysis depicted a significant difference in terms of hypoxaemia (p=0.01) and severe hypoxaemia (p=0.0003) occurrence between groups in favour of the automated group. 25 patients experienced hypoxaemia for >10% of the entire monitoring time during the 3 days within the standard group, as compared to the automated group (p<0.0001). CONCLUSION: Automated closed-loop oxygen administration promotes greater time within the oxygenation target, as compared to standard manual administration, thus reducing the occurrence of hypoxaemia and hyperoxaemia.

Physiological effects of mixed-gas deep sea dives using a closed-circuit rebreather: a field pilot study.

PURPOSE: Deep diving using mixed gas with closed-circuit rebreathers (CCRs) is increasingly common. However, data regarding the effects of these dives are still scarce. This preliminary field study aimed at evaluating the acute effects of deep (90-120 msw) mixed-gas CCR bounce dives on lung function in relation with other physiological parameters. METHODS: Seven divers performed a total of sixteen open-sea CCR dives breathing gas mixture of helium, nitrogen and oxygen (trimix) within four days at 2 depths (90 and 120 msw). Spirometric parameters, SpO2, body mass, hematocrit, short term heart rate variability (HRV) and critical flicker fusion frequency (CFFF) were measured at rest 60 min before the dive and 120 min after surfacing. RESULTS: The median [1st-3rd quartile] of the forced vital capacity was lower (84% [76-93] vs 91% [74-107] of predicted values; p = 0.029), whereas FEV1/FVC was higher (98% [95-99] vs 95% [89-99]; p = 0.019) after than before the dives. The other spirometry values and SpO2 were unchanged. Body mass decreased from 73.5 kg (72.0-89.6) before the dives to 70.0 kg (69.2-85.8) after surfacing (p = 0.001), with no change of hematocrit or CFFT. HRV was increased as indicated by the higher SDNN, RMSSD and pNN50 after than before dives. CONCLUSION: The present observation represents the first original data regarding the effects of deep repeated CCR dives. The body mass loss and decrease of FVC after bounce dives at depth of about 100 msw may possibly impose an important physiological stress for the divers.

COVID-19: Pulse oximeters in the spotlight.

From home to intensive care units, innovations in pulse oximetry are susceptible to improve the monitoring and management of patients developing acute respiratory failure, and particularly those with the coronavirus disease 2019 (COVID-19). They include self-monitoring of oxygen saturation (SpO2) from home, continuous wireless SpO2 monitoring on hospital wards, and the integration of SpO2 as the input variable for closed-loop oxygen administration systems. The analysis of the pulse oximetry waveform may help to quantify respiratory efforts and prevent intubation delays. Tracking changes in the peripheral perfusion index during a preload-modifying maneuver may be useful to predict preload responsiveness and rationalize fluid therapy.

Automated O2 titration improves exercise capacity in patients with hypercapnic chronic obstructive pulmonary disease: a randomised controlled cross-over trial.

Automatically titrated O2 flows (FreeO2) was compared with constant O2 flow on exercise capacity, O2 saturation and risk of hyperoxia-related hypercapnia in patients with severe COPD with baseline hypercapnia and long-term oxygen therapy (LTOT). Twelve patients were enrolled in a randomised double-blind cross-over study to perform exercise with either FreeO2 or constant flow. Endurance time (primary outcome) and SpO2 were both significantly improved with FreeO2compared with constant flow (p<0.04), although pCO2 was similar in both conditions. Automated titration of O2 significantly and clinically improved endurance walking time in patients with severe COPD receiving LTOT, without worsening of pCO2 TRIAL REGISTRATION NUMBER: Results , NCT01575327.

Automatic versus manual oxygen administration in the emergency department.

Oxygen is commonly administered in hospitals, with poor adherence to treatment recommendations.We conducted a multicentre randomised controlled study in patients admitted to the emergency department requiring O2 ≥3 L·min-1 Patients were randomised to automated closed-loop or manual O2 titration during 3 h. Patients were stratified according to arterial carbon dioxide tension (PaCO2 ) (hypoxaemic PaCO2 ≤45 mmHg; or hypercapnic PaCO2 >45-≤55 mmHg) and study centre. Arterial oxygen saturation measured by pulse oximetry (SpO2 ) goals were 92-96% for hypoxaemic, or 88-92% for hypercapnic patients. Primary outcome was % time within SpO2 target. Secondary endpoints were hypoxaemia and hyperoxia prevalence, O2 weaning, O2 duration and hospital length of stay.187 patients were randomised (93 automated, 94 manual) and baseline characteristics were similar between the groups. Time within the SpO2 target was higher under automated titration (81±21% versus 51±30%, p<0.001). Time with hypoxaemia (3±9% versus 5±12%, p=0.04) and hyperoxia under O2 (4±9% versus 22±30%, p<0.001) were lower with automated titration. O2 could be weaned at the end of the study in 14.1% versus 4.3% patients in the automated and manual titration group, respectively (p<0.001). O2 duration during the hospital stay was significantly reduced (5.6±5.4 versus 7.1±6.3 days, p=0.002).Automated O2 titration in the emergency department improved oxygenation parameters and adherence to guidelines, with potential clinical benefits.

Development of a clinical prediction score for congestive heart failure diagnosis in the emergency care setting: The Brest score.

OBJECTIVE: To derive and validate a clinical prediction rule of acute congestive heart failure obtainable in the emergency care setting. DESIGN: Derivation of the score was performed on a retrospective 927 patients cohort admitted to our Emergency Department for dyspnea. The prediction model was externally validated on an independent 206-patient prospective cohort. INTERVENTIONS AND MEASURES: During the derivation phase, variables associated with acute congestive heart failure were included in a multivariate regression model. Logistic regression coefficients were used to assign scoring points to each variable. During the validation phase, every diagnosis was confirmed by an independent adjudication committee. RESULTS: The score comprised 11 variables: age ≥65 years (1 point), seizure dyspnea (2 points), night outbreak (1 point), orthopnea (1 point), history of pulmonary edema (2 points), chronic pulmonary disease (-2 points), myocardial infarction (1 point), crackles (2 points), leg edema (1 point), ST-segment abnormality (1 point), atrial fibrillation/flutter (1 point) on electrocardiography. In the validation step, 30 patients (14.6%) had a low clinical probability of acute congestive heart failure (score ≤3), of which only 2 (6.7%) had a proven acute cardiogenic pulmonary edema. The prevalence of acute congestive heart failure was 58.5% in the 94 patients with an intermediate probability (score of 4-8) and 91.5% in the 82 patients (39.8%) with a high probability (score ≥9). CONCLUSION: This score of acute congestive heart failure based on easily available and objective variables is entirely standardized. Applying the score to dyspneic adult emergency patients may enable a more rapid and efficient diagnostic process.

Routine biological tests in self-poisoning patients: results from an observational prospective multicenter study.

CONTEXT: Routine biological tests are frequently ordered in self-poisoning patients, but their clinical relevance is poorly studied. MATERIALS AND METHODS: This is a prospective multicentric observational study conducted in the emergency departments and intensive care units of 5 university and nonuniversity French hospitals. Adult self-poisoning patients without severely altered vital status on admission were prospectively included. RESULTS: Routine biological test (serum electrolytes and creatinine, liver enzymes, bilirubin, blood cell count, prothrombin time) ordering and results were analyzed. A total of 1027 patients were enrolled (age, 40.2 ± 14 years; women, 61.5%); no patient died during the hospital stay. Benzodiazepine was suspected in more than 70% of cases; 65% (range, 48%-80%) of patients had at least 1 routine biological test performed. At least 1 abnormal test was registered in 23% of these patients. Three factors were associated with abnormal test results: age older than 40 years, male sex, and poisoning with a drug known to alter routine tests (ie, acetaminophen, NSAIDs, metformine, lithium). Depending on these factors, abnormal results ranged from 14% to 48%. Unexpected severe life-threatening conditions were recorded in 6 patients. Only 3 patients were referred to the intensive care unit solely because of abnormal test results. CONCLUSION: Routine biological tests are commonly prescribed in nonsevere self-poisoning patients. Abnormal results are frequent but their relevance at bedside remains limited.

Acquiring procedural skills in ICUs: a prospective multicenter study*.

OBJECTIVES: Providing appropriate training of procedural skills to residents while ensuring patient safety through trainee supervision is a difficult and constant challenge. We sought to determine how effective and safe procedural skill acquisition is in French ICUs and to identify failure and complication risk factors. DESIGN: Multicenter prospective observational study. Invasive procedures performed by residents were recorded during two consecutive semesters. SETTING: Eighty-four residents. SUBJECTS: Eighty-four residents. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Number of invasive procedures performed, failure and complication rates, supervision, and assistance provided. Five thousand six hundred seventeen procedures were prospectively studied: 1,007 tracheal intubations, 1,272 arterial and 2,586 central venous catheter insertions, 457 fiberoptic bronchoscopies, and 295 chest tube insertions. During the semesters, residents performed a median of 10 intubations, 14 arterial catheter insertions, and 26 central venous catheter insertions. Complication rates were low, similar to those in the literature: 8.6% desaturation and 7.4% esophageal placement during intubation; 0.4% and 2.3% pneumothorax with jugular and subclavian central venous catheter insertions, respectively. We identified risk factors for failure and complications. Higher rates of failure and complications for intubation were associated with residents with no or little previous experience (p < 0.001); failure of internal jugular vein catheterization was associated with left-side insertion (p = 0.005) and absence of mechanical ventilation (p = 0.007). Supervision and assistance were more frequent at the beginning of the semester and for intubation and chest tube insertion. Finally, residents had less access to fiberoptic bronchoscopy and chest tube insertion. CONCLUSION: Procedural skills acquisition by residents in the ICU appears feasible and safe with complication rates comparable to what has previously been reported. We identified specific procedures and situations associated with higher failure and complication rates that could require proactive training. Questions still remain regarding minimal numbers of procedures to attain competence and how best to provide procedural training.

Bench-test comparison of 26 emergency and transport ventilators.

INTRODUCTION: Numerous emergency and transport ventilators are commercialized and new generations arise constantly. The aim of this study was to evaluate a large panel of ventilators to allow clinicians to choose a device, taking into account their specificities of use. METHODS: This experimental bench-test took into account general characteristics and technical performances. Performances were assessed under different levels of FIO2 (100%, 50% or Air-Mix), respiratory mechanics (compliance 30,70,120 mL/cmH2O; resistance 5,10,20 cmH2O/mL/s), and levels of leaks (3.5 to 12.5 L/min), using a test lung. RESULTS: In total 26 emergency and transport ventilators were analyzed and classified into four categories (ICU-like, n = 5; Sophisticated, n = 10; Simple, n = 9; Mass-casualty and military, n = 2). Oxygen consumption (7.1 to 15.8 L/min at FIO2 100%) and the Air-Mix mode (FIO2 45 to 86%) differed from one device to the other. Triggering performance was heterogeneous, but several sophisticated ventilators depicted triggering capabilities as efficient as ICU-like ventilators. Pressurization was not adequate for all devices. At baseline, all the ventilators were able to synchronize, but with variations among respiratory conditions. Leak compensation in most ICU-like and 4/10 sophisticated devices was able to correct at least partially for system leaks, but with variations among ventilators. CONCLUSION: Major differences were observed between devices and categories, either in terms of general characteristics or technical reliability, across the spectrum of operation. Huge variability of tidal volume delivery with some devices in response to modifications in respiratory mechanics and FIO2 should make clinicians question their use in the clinical setting.