Clinical implementation of automated O2 titration in a tertiary care hospital.

Background: When treating acute respiratory failure, both hypoxemia and hyperoxemia should be avoided. SpO2 should be monitored closely and O2 flows adjusted accordingly. Achieving this goal might be easier with automated O2 titration compared to manual titration of fixed-flow O2 We evaluated the feasibility of using an automated O2 titration device in subjects treated for acute hypoxemic respiratory failure in a tertiary care hospital.Methods: Healthcare workers received education and training about oxygen therapy and were familiarized with an automated O2 titration device (FreeO2, Oxynov, Quebec City, Canada). A coordinator was available from 8 am to 5 pm during week days to provide technical assistance. The ability of the device to maintain SpO2 within the prescribed therapeutic window was recorded. Basic clinical information was recorded.Results: Subjects were enrolled from November 2020 to August 2022. We trained 508 healthcare workers on use of automated O2 titration which was finally used on 872 occasions in 763 subjects, distributed on the respiratory, COVID-19 and thoracic surgery wards and the emergency room. Clinical information could be retrieved for 609 (80%) subjects who were on the system for a median of 3 days (interquartile range: 2 to 6 days) representing 2567 subject-days of clinical experience with the device. In the 82 (14%) subjects for whom this information was available, the system maintained SpO2 within the prescribed targets 89% of the time. Ninety-six subjects experienced clinical deterioration as defined by the need to be transferred to the intensive care unit and/or requirement of high nasal flow oxygen but none of these events were judged to be related to the O2 device.Conclusions: Automated O2 titration could be successfully implemented in hospitalized subjects with hypoxemic respiratory failure from various causes. This experience should foster further improvement of the device and recommendations for an optimized utilization.

Evaluation of the Humidification Performances of New Generation of Heated Wire Humidifiers.

BACKGROUND: At high ambient temperatures in ICU rooms, the humidification performances of heated-wire humidifiers are significantly reduced, with delivered gas humidity well below 30 mg H2O/L, which leads to an increased risk of endotracheal occlusions, subocclusions, or mucociliary dysfunction. The objective of the study was to evaluate the humidity delivered at the Y-piece with new-generation heated-wire humidifiers with advanced algorithm (FP950 [Fisher & Paykel Healthcare, Auckland, New Zealand] and VHB20 [Vincent Medical, Inspired, Hong Kong]) while varying ambient temperatures. METHODS: We measured, on the bench, the hygrometry of inspiratory gases delivered by a new generation of heated-wire humidifiers (i) FP950, (ii) VHB20 and a previous generation of heated-wire humidifiers, (iii) MR850 (Fisher & Paykel) with the usual settings (37°C at the chamber/40°C at the Y-piece), (iv) MR850 with no temperature gradient (40°C/40°C), and (v) MR850 with the automatic compensation algorithm activated. Hygrometry was measured with the psychrometric method after 1 h of stability while varying the room temperature from 20 to 30°C. RESULTS: Two hundred ninety-four hygrometric bench measurements were performed at steady state for the different tested conditions. With the new heated-wire humidifiers (FP950 and VHB20), gas humidity delivered remained > 30 mg H2O/L in all tested conditions, even at high ambient temperatures (>25°C). With previous generations of heated-wire humidifiers (MR850), at high ambient temperature, humidity delivered was adequate in only 26% (11/42) of the measurements when the usual settings were used (37°C/40°C) and 30% (11/37) with automatic compensation. When no temperature gradient was set (40°C/40°C), humidity delivered was > 30 mg H2O/L in 91% (30/33) of the measurements at a high ambient temperature. With an ambient temperature < 25°C, almost all devices and settings provided adequate humidity. CONCLUSIONS: The new FP950 and VHB20 heated-wire humidifiers by using advanced algorithms demonstrated stable performance while varying the ambient temperature by 20-30°C, better than the previous generation of heated humidifiers when ambient temperatures were high.

Ozanimod Therapy in Patients With COVID-19 Requiring Oxygen Support: A Randomized, Open-Label, Pilot Trial.

BACKGROUND: Sphingosine-1-phosphate receptor ligands (SRLs) dampen immunopathologic damages in models of viral pneumonia. RESEARCH QUESTION: Is it feasible to administer an SRL therapy, here ozanimod (OZA), to acutely ill patients infected with SARS-CoV-2? STUDY DESIGN AND METHODS: The prospective, randomized, open-label, COVID-19 Ozanimod Intervention (COZI) pilot trial was conducted in three Canadian hospitals. Patients admitted for COVID-19 requiring oxygen were eligible. Randomization was stratified for risk factors of poor outcome and oxygen needs at inclusion. Participants were allocated to standard of care (SOC) or to SOC plus OZA. OZA (oral, once daily, incremental dosage) was administered for a maximum of 14 days. Primary end point investigated for size effect and variance over time was the assessment of safety and efficacy, evaluated by the daily score on the World Health Organization-adapted six-point ordinal scale for clinical improvement analyzed under the intention-to-treat principle. RESULTS: Twenty-three patients were randomized to the SOC arm, and 20 were randomized to the OZA arm from September 2020 to February 2022. Evaluation of efficacy showed nonsignificant reductions of median duration of respiratory support (6 [range, 3-10] vs 9 [range, 4-12] days; P = .34), median duration of hospitalization (9 [range, 6-12] vs 10 [range, 6-18] days; P = .20), and median time to clinical improvement (4 [range, 3-7] vs 7 [range, 3-11] days; P = .12) for OZA compared with SOC, respectively. Heart rate was significantly lower with OZA (65 [range, 63-67] vs 71 [range, 69-72] beats/min; P < .0001). However, QT and PR intervals were not affected. No severe adverse drug reaction was reported. INTERPRETATION: To our knowledge, SRL utility in severe pneumonia has never been tested in patients. We show for the first time that this new pharmacologic agent can safely be administered to patients hospitalized for viral pneumonia, with potential clinical benefits. Bradycardia was frequent but well tolerated. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT04405102; URL: www. CLINICALTRIALS: gov.

Small-Volume Blood Collection Tubes to Reduce Transfusions in Intensive Care: The STRATUS Randomized Clinical Trial.

Importance: Blood collection for laboratory testing in intensive care unit (ICU) patients is a modifiable contributor to anemia and red blood cell (RBC) transfusion. Most blood withdrawn is not required for analysis and is discarded. Objective: To determine whether transitioning from standard-volume to small-volume vacuum tubes for blood collection in ICUs reduces RBC transfusion without compromising laboratory testing procedures. Design, Setting, and Participants: Stepped-wedge cluster randomized trial in 25 adult medical-surgical ICUs in Canada (February 5, 2019 to January 21, 2021). Interventions: ICUs were randomized to transition from standard-volume (n = 10 940) to small-volume tubes (n = 10 261) for laboratory testing. Main Outcomes and Measures: The primary outcome was RBC transfusion (units per patient per ICU stay). Secondary outcomes were patients receiving at least 1 RBC transfusion, hemoglobin decrease during ICU stay (adjusted for RBC transfusion), specimens with insufficient volume for testing, length of stay in the ICU and hospital, and mortality in the ICU and hospital. The primary analysis included patients admitted for 48 hours or more, excluding those admitted during a 5.5-month COVID-19-related trial hiatus. Results: In the primary analysis of 21 201 patients (mean age, 63.5 years; 39.9% female), which excluded 6210 patients admitted during the early COVID-19 pandemic, there was no significant difference in RBC units per patient per ICU stay (relative risk [RR], 0.91 [95% CI, 0.79 to 1.05]; P = .19; absolute reduction of 7.24 RBC units/100 patients per ICU stay [95% CI, -3.28 to 19.44]). In a prespecified secondary analysis (n = 27 411 patients), RBC units per patient per ICU stay decreased after transition from standard-volume to small-volume tubes (RR, 0.88 [95% CI, 0.77 to 1.00]; P = .04; absolute reduction of 9.84 RBC units/100 patients per ICU stay [95% CI, 0.24 to 20.76]). Median decrease in transfusion-adjusted hemoglobin was not statistically different in the primary population (mean difference, 0.10 g/dL [95% CI, -0.04 to 0.23]) and lower in the secondary population (mean difference, 0.17 g/dL [95% CI, 0.05 to 0.29]). Specimens with insufficient quantity for analysis were rare (≤0.03%) before and after transition. Conclusions and Relevance: Use of small-volume blood collection tubes in the ICU may decrease RBC transfusions without affecting laboratory analysis. Trial Registration: ClinicalTrials.gov Identifier: NCT03578419.

Automated O2 Titration Alone or With High-Flow Nasal Cannula During Walking Exercise in Chronic Lung Diseases.

BACKGROUND: Exercise-induced O2 desaturation contributes to dyspnea and exercise intolerance in various respiratory diseases. This study assessed whether automated O2 titration was superior to fixed-flow O2 to improve exertional dyspnea and walking exercise endurance. We also aimed at evaluating possible additive effects of high-flow nasal cannula coupled with automated O2 titration on these outcomes. METHODS: Subjects with chronic respiratory diseases and exercise-induced desaturation performed a 3-min constant-speed shuttle test (CSST) and an endurance shuttle walking test (ESWT) with either (1) fixed-flow O2, (2) automated O2 titration targeting an SpO2 of 94% (± 2%), and (3) automated O2 titration + high-flow nasal cannula according to a randomized sequence. The main outcome was Borg dyspnea score at the end of the 3-min CSST. Secondary outcomes included endurance time and dyspnea during ESWT and oxygenation status during exercise. RESULTS: Ten subjects with COPD, 10 with interstitial lung disease, 5 with pulmonary hypertension, and 3 with cystic fibrosis completed the study. Compared to fixed-flow O2, automated O2 titration did not reduce dyspnea at the end of the 3-min CSST. Endurance time during the ESWT was prolonged with automated O2 titration (mean difference 298 [95% CI 205-391] s, P < .001), and dyspnea at isotime was reduced. No further improvement was noted when high-flow nasal cannula was added to automated O2 titration. Compared to fixed-flow O2, O2 flows were higher with automated O2 titration, resulting in better oxygenation. CONCLUSIONS: Automated O2 titration was superior to fixed-flow O2 to alleviate dyspnea and improve exercise endurance during the ESWT in subjects with a variety of chronic respiratory diseases. Adding high-flow nasal cannula to automated O2 titration provided no further benefits.

Automated Oxygen Titration During CPAP and Noninvasive Ventilation in Healthy Subjects With Induced Hypoxemia.

BACKGROUND: Automated oxygen titration to maintain a stable SpO2 has been developed for spontaneously breathing patients but has not been evaluated during CPAP and noninvasive ventilation (NIV). METHODS: We performed a randomized controlled crossover, double-blind study on 10 healthy subjects with induced hypoxemia during 3 situations: spontaneous breathing with oxygen support, CPAP (5 cm H2O), and NIV (7/3 cm H2O). We conducted in random order 3 dynamic hypoxic challenges of 5 min (FIO2 0.08 ± 0.02, 0.11± 0.02, and 0.14 ± 0.02). For each condition, we compared automated oxygen titration and manual oxygen titration by experienced respiratory therapists (RTs), with the aim to maintain the SpO2 at 94 ± 2%. In addition, we included 2 subjects hospitalized for exacerbation of COPD under NIV and a subject managed after bariatric surgery with CPAP and automated oxygen titration. RESULTS: The percentage of time in the SpO2 target was higher with automated compared with manual oxygen titration for all conditions, on average 59.6 ± 22.8% compared to 44.3 ± 23.9% (P = .004). Hyperoxemia (SpO2 > 96%) was less frequent with automated titration for each mode of oxygen administration (24.0 ± 24.4% vs 39.1 ± 25.3%, P < .001). During the manual titration periods, the RT made several changes to oxygen flow (5.1 ± 3.3 interventions that lasted 122 ± 70 s/period) compared to none during the automated titration to maintain oxygenation in the targeted SpO2 . Time in the SpO2 target was higher with stable hospitalized subjects in comparison with healthy subjects under dynamic-induced hypoxemia. CONCLUSIONS: In this proof-of-concept study, automated oxygen titration was used during CPAP and NIV. The performances to maintain the SpO2 target were significantly better compared to manual oxygen titration in the setting of this study protocol. This technology may allow decreasing the number of manual interventions for oxygen titration during CPAP and NIV.

Study protocol for a randomized controlled trial of Proportional Assist Ventilation for Minimizing the Duration of Mechanical Ventilation: the PROMIZING study.

BACKGROUND: Proportional assist ventilation with load-adjustable gain factors (PAV+) is a mechanical ventilation mode that delivers assistance to breathe in proportion to the patient's effort. The proportional assistance, called the gain, can be adjusted by the clinician to maintain the patient's respiratory effort or workload within a normal range. Short-term and physiological benefits of this mode compared to pressure support ventilation (PSV) include better patient-ventilator synchrony and a more physiological response to changes in ventilatory demand. METHODS: The objective of this multi-centre randomized controlled trial (RCT) is to determine if, for patients with acute respiratory failure, ventilation with PAV+ will result in a shorter time to successful extubation than with PSV. This multi-centre open-label clinical trial plans to involve approximately 20 sites in several continents. Once eligibility is determined, patients must tolerate a short-term PSV trial and either (1) not meet general weaning criteria or (2) fail a 2-min Zero Continuous Positive Airway Pressure (CPAP) Trial using the rapid shallow breathing index, or (3) fail a spontaneous breathing trial (SBT), in this sequence. Then, participants in this study will be randomized to either PSV or PAV+ in a 1:1 ratio. PAV+ will be set according to a target of muscular pressure. The weaning process will be identical in the two arms. Time to liberation will be the primary outcome; ventilator-free days and other outcomes will be measured. DISCUSSION: Meta-analyses comparing PAV+ to PSV suggest PAV+ may benefit patients and decrease healthcare costs but no powered study to date has targeted the difficult to wean patient population most likely to benefit from the intervention, or used consistent timing for the implementation of PAV+. Our enrolment strategy, primary outcome measure, and liberation approaches may be useful for studying mechanical ventilation and weaning and can offer important results for patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT02447692 . Prospectively registered on May 19, 2015.

Accuracy of Multiple Pulse Oximeters in Stable Critically Ill Patients.

BACKGROUND: An accurate SpO2 value is critical in order to optimally titrate oxygen delivery to patients and to follow oxygenation guidelines. Limited prospective data exist on real-world performance of pulse oximeters in critically ill patients. The objective of this study was to assess accuracy and bias of the SpO2 values measured by several oximeters in hospitalized subjects. METHODS: We included stable adults in the ICU with an arterial catheter in place. Main exclusion criteria were poor SpO2 signal and SpO2 > 96%. In each subject, we simultaneously evaluated 4 oximeters: Nonin (Plymouth, Minnesota) embedded in the FreeO2 device (OxyNov, Québec City, Québec, Canada), Masimo (Radical-7, Masimo, Irvine, California), Philips (FAST, Philips, Amsterdam, the Netherlands), and Nellcor (N-600, Medtronic, Minneapolis, Minnesota). Arterial blood gases were drawn and simultaneously each oximeters' SpO2 values were collected. SpO2 values were compared to the reference (arterial oxygen saturation [SaO2 ] value) to determine bias and accuracy. The ability for oximeters to detect hypoxemia and the impact of oximeters on oxygen titration were evaluated. RESULTS: We included 193 subjects (153 male, mean age 66 y) in whom 211 sets of measurements were performed. The skin pigmentation evaluated by Fitzpatrick scale showed 96.2% of subjects were light skin (types 1 and 2). One oximeter overestimated SaO2 (Philips, +0.9%), whereas the 3 others underestimated SaO2 (Nonin -3.1%, Nellcor -0.3%, Masimo -0.2%). SaO2 was underestimated with Nonin oximeter in 91.3% of the cases, whereas it was overestimated in 55.2% of the cases with Philips oximeter. Moderate hypoxemia (SaO2 86-90% or PaO2 55-60 mm Hg) was detected in 92, 33, 42, and 11% of the cases with Nonin, Nellcor, Masimo, and Philips, respectively. CONCLUSIONS: We found significant bias and moderate accuracy between the tested oximeters and the arterial blood gases in the studied population. These discrepancies may have important clinical impact on the detection of hypoxemia and management of oxygen therapy.

Monitoring of Heated Wire Humidifier Hygrometric Performances With Heater Plate Temperature.

BACKGROUND: Under-humidification and associated complications may occur with heated humidifiers. Hygrometric performances of heated wire humidifiers are reduced by high ambient and high outlet ventilator temperatures. Currently, there is no reliable monitoring tool to evaluate humidification performances of heated wire humidifiers in the daily practice. We sought to demonstrate the relation between humidity delivered by heated wire humidifiers and different parameters that could be used to monitor humidity of gas delivered to subjects. METHODS: On a bench test, we measured heater plate temperature, inlet chamber temperature, and delivered humidity with MR850 system. Temperature displayed on the humidifier was also recorded. The measurements were performed at different ambient temperatures and five minute ventilation levels (5, 7.5, 10, 12.5, 15 L/min). Inlet chamber temperatures varied from 20-40°C. In each condition, hygrometric measurements with the psychrometric method were performed at steady state. RESULTS: We performed 279 measurements at steady state including all conditions. We found a good correlation between heater plate temperature and absolute humidity delivered (R2 = 0.82). This relationship was hardly affected by ambient temperature, but minute ventilation had more effect. For different minute ventilations, the correlation between heater plate temperature and absolute humidity delivered was very good with coefficient of determination R2 from 0.87-0.98. Heater plate temperature > 62°C was a good predictor of absolute humidity delivered > 30 mg H2O/L (area under the curve = 0.96, sensibility 79%, specificity 94%). No correlation existed between humidity delivered and the outlet chamber temperature (displayed on the humidifier). CONCLUSIONS: In this bench study, we have shown a good correlation between heater plate temperature and humidity delivered with a heated wire humidifier. This means that a "hidden" hygrometer is built into the heated wire humidifier. Heater plate temperature should be used as a surrogate of humidity to improve the humidification monitoring.

The PROMIZING trial enrollment algorithm for early identification of patients ready for unassisted breathing.

BACKGROUND: Liberating patients from mechanical ventilation (MV) requires a systematic approach. In the context of a clinical trial, we developed a simple algorithm to identify patients who tolerate assisted ventilation but still require ongoing MV to be randomized. We report on the use of this algorithm to screen potential trial participants for enrollment and subsequent randomization in the Proportional Assist Ventilation for Minimizing the Duration of MV (PROMIZING) study. METHODS: The algorithm included five steps: enrollment criteria, pressure support ventilation (PSV) tolerance trial, weaning criteria, continuous positive airway pressure (CPAP) tolerance trial (0 cmH2O during 2 min) and spontaneous breathing trial (SBT): on fraction of inspired oxygen (FiO2) 40% for 30-120 min. Patients who failed the weaning criteria, CPAP Zero trial, or SBT were randomized. We describe the characteristics of patients who were initially enrolled, but passed all steps in the algorithm and consequently were not randomized. RESULTS: Among the 374 enrolled patients, 93 (25%) patients passed all five steps. At time of enrollment, most patients were on PSV (87%) with a mean (± standard deviation) FiO2 of 34 (± 6) %, PSV of 8.7 (± 2.9) cmH2O, and positive end-expiratory pressure of 6.1 (± 1.6) cmH2O. Minute ventilation was 9.0 (± 3.1) L/min with a respiratory rate of 17.4 (± 4.4) breaths/min. Patients were liberated from MV with a median [interquartile range] delay between initial screening and extubation of 5 [1-49] hours. Only 7 (8%) patients required reintubation. CONCLUSION: The trial algorithm permitted identification of 93 (25%) patients who were ready to extubate, while their clinicians predicted a duration of ventilation higher than 24 h.

Early heart rate variability evaluation enables to predict ICU patients' outcome.

Heart rate variability (HRV) is a mean to evaluate cardiac effects of autonomic nervous system activity, and a relation between HRV and outcome has been proposed in various types of patients. We attempted to evaluate the best determinants of such variation in survival prediction using a physiological data-warehousing program. Plethysmogram tracings (PPG) were recorded at 75 Hz from the standard monitoring system, for a 2 h period, during the 24 h following ICU admission. Physiological data recording was associated with metadata collection. HRV was derived from PPG in either the temporal and non-linear domains. 540 consecutive patients were recorded. A lower LF/HF, SD2/SD1 ratios and Shannon entropy values on admission were associated with a higher ICU mortality. SpO2/FiO2 ratio and HRV parameters (LF/HF and Shannon entropy) were independent correlated with mortality in the multivariate analysis. Machine-learning using neural network (kNN) enabled to determine a simple decision tree combining the three best determinants (SDNN, Shannon Entropy, SD2/SD1 ratio) of a composite outcome index. HRV measured on admission enables to predict outcome in the ICU or at Day-28, independently of the admission diagnosis, treatment and mechanical ventilation requirement.Trial registration: ClinicalTrials.gov identifier NCT02893462.

Impact of Airway Humidification Strategy in Mechanically Ventilated COVID-19 Patients.

BACKGROUND: Humidification of inspiratory gases is mandatory in all mechanically ventilated patients in ICUs, either with heated humidifiers (HHs) or with heat and moisture exchangers (HMEs). In patients with COVID-19, the choice of the humidification device may have relevant impact on patients' management as demonstrated in recent studies. We reported data from 2 ICUs using either HME or HH. METHODS: Data from patients with COVID-19 requiring invasive mechanical ventilation during the first wave in 2 ICUs in Québec City were reviewed. In one ICU, HMEs were used, whereas heated-wire HHs were used in the other ICU. We compared ventilator settings and arterial blood gases at day one after adjustment of ventilator settings. Episodes of endotracheal tube occlusions (ETOs) or subocclusions and a strategy to limit the risk of under-humidification were reported. On a bench test, we measured humidity with psychrometry with HH at different ambient temperature and evaluated the relation with heater plate temperature. RESULTS: We reported data from 20 subjects positive for SARS-Cov-2, including 6 in the ICU using HME and 14 in the ICU using HH. In the HME group, PaCO2 was higher (48 vs 42 mm Hg) despite higher minute ventilation (171 vs 145 mL/kg/min predicted body weight [PBW]). We also reported 3 ETOs occurring in the ICU using HH. The hygrometric bench study reported a strong correlation between heater plate temperatures of the HH and humidity delivered. After implementation of measures to avoid under-humidification, including heater plate temperature monitoring, no more ETOs occurred. CONCLUSIONS: The choice of the humidification device used in subjects with COVID-19 had a relevant impact on ventilation efficiency (increased CO2 removal with lower dead space) and on complications related to low humidity, including ETOs that may be present with heated-wire HHs when used with high ambient temperatures.

Effect of Probiotics on Incident Ventilator-Associated Pneumonia in Critically Ill Patients: A Randomized Clinical Trial.

Importance: Growing interest in microbial dysbiosis during critical illness has raised questions about the therapeutic potential of microbiome modification with probiotics. Prior randomized trials in this population suggest that probiotics reduce infection, particularly ventilator-associated pneumonia (VAP), although probiotic-associated infections have also been reported. Objective: To evaluate the effect of Lactobacillus rhamnosus GG on preventing VAP, additional infections, and other clinically important outcomes in the intensive care unit (ICU). Design, Setting, and Participants: Randomized placebo-controlled trial in 44 ICUs in Canada, the United States, and Saudi Arabia enrolling adults predicted to require mechanical ventilation for at least 72 hours. A total of 2653 patients were enrolled from October 2013 to March 2019 (final follow-up, October 2020). Interventions: Enteral L rhamnosus GG (1 × 1010 colony-forming units) (n = 1321) or placebo (n = 1332) twice daily in the ICU. Main Outcomes and Measures: The primary outcome was VAP determined by duplicate blinded central adjudication. Secondary outcomes were other ICU-acquired infections including Clostridioides difficile infection, diarrhea, antimicrobial use, ICU and hospital length of stay, and mortality. Results: Among 2653 randomized patients (mean age, 59.8 years [SD], 16.5 years), 2650 (99.9%) completed the trial (mean age, 59.8 years [SD], 16.5 years; 1063 women [40.1%.] with a mean Acute Physiology and Chronic Health Evaluation II score of 22.0 (SD, 7.8) and received the study product for a median of 9 days (IQR, 5-15 days). VAP developed among 289 of 1318 patients (21.9%) receiving probiotics vs 284 of 1332 controls (21.3%; hazard ratio [HR], 1.03 (95% CI, 0.87-1.22; P = .73, absolute difference, 0.6%, 95% CI, -2.5% to 3.7%). None of the 20 prespecified secondary outcomes, including other ICU-acquired infections, diarrhea, antimicrobial use, mortality, or length of stay showed a significant difference. Fifteen patients (1.1%) receiving probiotics vs 1 (0.1%) in the control group experienced the adverse event of L rhamnosus in a sterile site or the sole or predominant organism in a nonsterile site (odds ratio, 14.02; 95% CI, 1.79-109.58; P < .001). Conclusions and Relevance: Among critically ill patients requiring mechanical ventilation, administration of the probiotic L rhamnosus GG compared with placebo, resulted in no significant difference in the development of ventilator-associated pneumonia. These findings do not support the use of L rhamnosus GG in critically ill patients. Trial Registration: ClinicalTrials.gov Identifier: NCT02462590.

Hygrometric Performances of Different High-Flow Nasal Cannula Devices: Bench Evaluation and Clinical Tolerance.

BACKGROUND: High-flow nasal cannula (HFNC) is increasingly used for the management of respiratory failure. Settings include [Formula: see text], total gas flow, and temperature target. Resulting absolute humidity (AH) at the nasal cannula may affect clinical tolerance, and optimal settings with respect to hygrometry remain poorly documented. METHODS: A bench study was designed to assess AH delivered by 4 HFNC devices (Optiflow, Airvo 2, Precision Flow, and Hydrate) according to flow, ambient temperature, and other available settings. Clinical tolerance of different levels of hygrometry (20, 30, and 40 mg H2O/L) was evaluated in 15 healthy volunteers. RESULTS: With [Formula: see text] set at 1.0, normal ambient temperature, and settings made accordingly to the manufacturers' recommendations, mean ± SD AH was 42.2 ± 3.1, 39.5 ± 1.8, 35.7 ± 2.0, and 32.9 ± 2.7 mg H2O/L for the Airvo 2, Optiflow, Hydrate, and Precision Flow, respectively, (P < .001). AH dropped from -3.5 to -10.7 mg H2O/L (P <. 001) with high ambient temperature, except for the Precision Flow. Increasing flow did not significantly affect AH except for the Precision Flow (from 36.4 ± 1.6 to 29.8 ± 0.2 mg H2O/L at 10 and 40 L/min, respectively, [P < .001]). The lowest AH was encountered with the Optiflow set with noninvasive ventilation (NIV) mode, without compensation algorithm, and at high ambient temperature (14.2 ± 1.5 mg H2O/L). In studied subjects, AH significantly affected breathing comfort, reduced from 7.0 ± 1.0 to 3.0 ± 2.0 at 40 and 20 mg H2O/L, respectively, (P < .001). Comfort was similar at 30 and 40 mg H2O/L. CONCLUSIONS: When used according to manufacturer's recommendations and at normal ambient temperature, all the HFNC devices evaluated achieved satisfactory hygrometric output with respect to breathing comfort evaluated in healthy subjects (≥ 30 mg H2O/L). Substantial differences exist between devices, and optimal knowledge of their working principles is required as inappropriate usage may dramatically alter efficacy and clinical tolerance.