High PEEP/low FiO2 ventilation is associated with lower mortality in COVID-19.

RATIONALE: The positive end-expiratory pressure (PEEP) strategy in patients with coronavirus 2019 (COVID-19) acute respiratory distress syndrome (ARDS) remains debated. Most studies originate from the initial waves of the pandemic. Here we aimed to assess the impact of high PEEP/low FiO2 ventilation on outcomes during the second wave in the Netherlands. METHODS: Retrospective observational study of invasively ventilated COVID-19 patients during the second wave. Patients were categorized based on whether they received high PEEP or low PEEP ventilation according to the ARDS Network tables. The primary outcome was ICU mortality, and secondary outcomes included hospital and 90-day mortality, duration of ventilation and length of stay, and the occurrence of kidney injury. Propensity matching was performed to correct for factors with a known relationship to ICU mortality. RESULTS: This analysis included 790 COVID-ARDS patients. At ICU discharge, 32 (22.5%) out of 142 high PEEP patients and 254 (39.2%) out of 848 low PEEP patients had died (HR 0.66 [0.46-0.96]; P = 0.03). High PEEP was linked to improved secondary outcomes. Matched analysis did not change findings. CONCLUSIONS: High PEEP ventilation was associated with improved ICU survival in patients with COVID-ARDS.

POStoperative INTELLiVENT-adaptive support VEntilation in cardiac surgery patients (POSITiVE) II-study protocol of a randomized clinical trial.

BACKGROUND: One single-center randomized clinical trial showed that INTELLiVENT-adaptive support ventilation (ASV) is superior to conventional ventilation with respect to the quality of ventilation in post-cardiac surgery patients. Other studies showed that this automated ventilation mode reduces the number of manual interventions at the ventilator in various types of critically ill patients. In this multicenter study in patients post-cardiac surgery, we test the hypothesis that INTELLiVENT-ASV is superior to conventional ventilation with respect to the quality of ventilation. METHODS: "POStoperative INTELLiVENT-adaptive support VEntilation in cardiac surgery patients II (POSITiVE II)" is an international, multicenter, two-group randomized clinical superiority trial. In total, 328 cardiac surgery patients will be randomized. Investigators screen patients aged > 18 years of age, scheduled for elective cardiac surgery, and expected to receive postoperative ventilation in the ICU for longer than 2 h. Patients either receive automated ventilation by means of INTELLiVENT-ASV or ventilation that is not automated by means of a conventional ventilation mode. The primary endpoint is quality of ventilation, defined as the proportion of postoperative ventilation time characterized by exposure to predefined optimal, acceptable, and critical (injurious) ventilatory parameters in the first two postoperative hours. One major secondary endpoint is ICU team staff workload, captured by the ventilator software collecting manual settings on alarms. Patient-centered endpoints include duration of postoperative ventilation and length of stay in ICU. DISCUSSION: POSITiVE II is the first international, multicenter, randomized clinical trial designed to confirm that POStoperative INTELLiVENT-ASV is superior to non-automated conventional ventilation and secondary to determine if this closed-loop ventilation mode reduces ICU team staff workload. The results of POSITiVE II will support intensive care teams in their choices regarding the use of automated ventilation in postoperative care of uncomplicated cardiac surgery patients. TRIAL REGISTRATION: Clinicaltrials.gov NCT06178510 . Registered on December 4, 2023.

Effect of automated versus conventional ventilation on mechanical power of ventilation-A randomized crossover clinical trial.

INTRODUCTION: Mechanical power of ventilation, a summary parameter reflecting the energy transferred from the ventilator to the respiratory system, has associations with outcomes. INTELLiVENT-Adaptive Support Ventilation is an automated ventilation mode that changes ventilator settings according to algorithms that target a low work-and force of breathing. The study aims to compare mechanical power between automated ventilation by means of INTELLiVENT-Adaptive Support Ventilation and conventional ventilation in critically ill patients. MATERIALS AND METHODS: International, multicenter, randomized crossover clinical trial in patients that were expected to need invasive ventilation > 24 hours. Patients were randomly assigned to start with a 3-hour period of automated ventilation or conventional ventilation after which the alternate ventilation mode was selected. The primary outcome was mechanical power in passive and active patients; secondary outcomes included key ventilator settings and ventilatory parameters that affect mechanical power. RESULTS: A total of 96 patients were randomized. Median mechanical power was not different between automated and conventional ventilation (15.8 [11.5-21.0] versus 16.1 [10.9-22.6] J/min; mean difference -0.44 (95%-CI -1.17 to 0.29) J/min; P = 0.24). Subgroup analyses showed that mechanical power was lower with automated ventilation in passive patients, 16.9 [12.5-22.1] versus 19.0 [14.1-25.0] J/min; mean difference -1.76 (95%-CI -2.47 to -10.34J/min; P < 0.01), and not in active patients (14.6 [11.0-20.3] vs 14.1 [10.1-21.3] J/min; mean difference 0.81 (95%-CI -2.13 to 0.49) J/min; P = 0.23). CONCLUSIONS: In this cohort of unselected critically ill invasively ventilated patients, automated ventilation by means of INTELLiVENT-Adaptive Support Ventilation did not reduce mechanical power. A reduction in mechanical power was only seen in passive patients. STUDY REGISTRATION: Clinicaltrials.gov (study identifier NCT04827927), April 1, 2021. URL OF TRIAL REGISTRY RECORD: https://clinicaltrials.gov/study/NCT04827927?term=intellipower&rank=1.

Effects of closed loop ventilation on ventilator settings, patient outcomes and ICU staff workloads - a systematic review.

BACKGROUND: Lung protective ventilation is considered standard of care in the intensive care unit. However, modifying the ventilator settings can be challenging and is time consuming. Closed loop modes of ventilation are increasingly attractive for use in critically ill patients. With closed loop ventilation, settings that are typically managed by the ICU professionals are under control of the ventilator's algorithms. OBJECTIVES: To describe the effectiveness, safety, efficacy and workload with currently available closed loop ventilation modes. DESIGN: Systematic review of randomised clinical trials. DATA SOURCES: A comprehensive systematic search in PubMed, Embase and the Cochrane Central register of Controlled Trials search was performed in January 2023. ELIGIBILITY CRITERIA: Randomised clinical trials that compared closed loop ventilation with conventional ventilation modes and reported on effectiveness, safety, efficacy or workload. RESULTS: The search identified 51 studies that met the inclusion criteria. Closed loop ventilation, when compared with conventional ventilation, demonstrates enhanced management of crucial ventilator variables and parameters essential for lung protection across diverse patient cohorts. Adverse events were seldom reported. Several studies indicate potential improvements in patient outcomes with closed loop ventilation; however, it is worth noting that these studies might have been underpowered to conclusively demonstrate such benefits. Closed loop ventilation resulted in a reduction of various aspects associated with the workload of ICU professionals but there have been no studies that studied workload in sufficient detail. CONCLUSIONS: Closed loop ventilation modes are at least as effective in choosing correct ventilator settings as ventilation performed by ICU professionals and have the potential to reduce the workload related to ventilation. Nevertheless, there is a lack of sufficient research to comprehensively assess the overall impact of these modes on patient outcomes, and on the workload of ICU staff.

Closed-loop ventilation in COVID-19 patients with acute hypoxemic respiratory failure-A case series.

BACKGROUND: INTELLiVENT-adaptive support ventilation (ASV) is an automated closed-loop mode of invasive ventilation for use in critically ill patients. INTELLiVENT-ASV automatically adjusts, without the intervention of the caregiver, ventilator settings to achieve the lowest work and force of breathing. AIMS: The aim of this case series is to describe the specific adjustments of INTELLiVENT-ASV in patients with acute hypoxemic respiratory failure, who were intubated for invasive ventilation. STUDY DESIGN: We describe three patients with severe acute respiratory distress syndrome (ARDS) because of COVID-19 who received invasive ventilation in our intensive care unit (ICU) in the first year of the COVID-19 pandemic. RESULTS: INTELLiVENT-ASV could be used successfully, but only after certain adjustments in the settings of the ventilator. Specifically, the high oxygen targets that are automatically chosen by INTELLiVENT-ASV when the lung condition 'ARDS' is ticked had to be lowered, and the titration ranges for positive end expiratory pressure (PEEP) and inspired oxygen fraction (FiO2 ) had to be narrowed. CONCLUSIONS: The challenges taught us how to adjust the ventilator settings so that INTELLiVENT-ASV could be used in successive COVID-19 ARDS patients, and we experienced the benefits of this closed-loop ventilation in clinical practice. RELEVANCE TO CLINICAL PRACTICE: INTELLiVENT-ASV is attractive to use in clinical practice. It is safe and effective in providing lung-protective ventilation. A closely observing user always remains needed. INTELLiVENT-ASV has a strong potential to reduce the workload associated with ventilation because of the automated adjustments.

A closed-loop ventilation mode that targets the lowest work and force of breathing reduces the transpulmonary driving pressure in patients with moderate-to-severe ARDS.

INTRODUCTION: The driving pressure (ΔP) has an independent association with outcome in patients with acute respiratory distress syndrome (ARDS). INTELLiVENT-Adaptive Support Ventilation (ASV) is a closed-loop mode of ventilation that targets the lowest work and force of breathing. AIM: To compare transpulmonary and respiratory system ΔP between closed-loop ventilation and conventional pressure controlled ventilation in patients with moderate-to-severe ARDS. METHODS: Single-center randomized cross-over clinical trial in patients in the early phase of ARDS. Patients were randomly assigned to start with a 4-h period of closed-loop ventilation or conventional ventilation, after which the alternate ventilation mode was selected. The primary outcome was the transpulmonary ΔP; secondary outcomes included respiratory system ΔP, and other key parameters of ventilation. RESULTS: Thirteen patients were included, and all had fully analyzable data sets. Compared to conventional ventilation, with closed-loop ventilation the median transpulmonary ΔP with was lower (7.0 [5.0-10.0] vs. 10.0 [8.0-11.0] cmH2O, mean difference - 2.5 [95% CI - 2.6 to - 2.1] cmH2O; P = 0.0001). Inspiratory transpulmonary pressure and the respiratory rate were also lower. Tidal volume, however, was higher with closed-loop ventilation, but stayed below generally accepted safety cutoffs in the majority of patients. CONCLUSIONS: In this small physiological study, when compared to conventional pressure controlled ventilation INTELLiVENT-ASV reduced the transpulmonary ΔP in patients in the early phase of moderate-to-severe ARDS. This closed-loop ventilation mode also led to a lower inspiratory transpulmonary pressure and a lower respiratory rate, thereby reducing the intensity of ventilation. Trial registration Clinicaltrials.gov, NCT03211494, July 7, 2017. https://clinicaltrials.gov/ct2/show/NCT03211494?term=airdrop&draw=2&rank=1 .

Effect of Automated Closed-loop ventilation versus convenTional VEntilation on duration and quality of ventilation in critically ill patients (ACTiVE) - study protocol of a randomized clinical trial.

BACKGROUND: INTELLiVENT-Adaptive Support Ventilation (ASV) is a fully automated closed-loop mode of ventilation for use in critically ill patients. Evidence for benefit of INTELLiVENT-ASV in comparison to ventilation that is not fully automated with regard to duration of ventilation and quality of breathing is largely lacking. We test the hypothesis that INTELLiVENT-ASV shortens time spent on a ventilator and improves the quality of breathing. METHODS: The "Effects of Automated Closed-loop VenTilation versus Conventional Ventilation on Duration and Quality of Ventilation" (ACTiVE) study is an international, multicenter, two-group randomized clinical superiority trial. In total, 1200 intensive care unit (ICU) patients with an anticipated duration of ventilation of > 24 h will be randomly assigned to one of the two ventilation strategies. Investigators screen patients aged 18 years or older at start of invasive ventilation in the ICU. Patients either receive automated ventilation by means of INTELLiVENT-ASV, or ventilation that is not automated by means of a conventional ventilation mode. The primary endpoint is the number of days free from ventilation and alive at day 28; secondary endpoints are quality of breathing using granular breath-by-breath analysis of ventilation parameters and variables in a time frame of 24 h early after the start of invasive ventilation, duration of ventilation in survivors, ICU and hospital length of stay (LOS), and mortality rates in the ICU and hospital, and at 28 and 90 days. DISCUSSION: ACTiVE is one of the first randomized clinical trials that is adequately powered to compare the effects of automated closed-loop ventilation versus conventional ventilation on duration of ventilation and quality of breathing in invasively ventilated critically ill patients. The results of ACTiVE will support intensivist in their choices regarding the use of automated ventilation. TRIAL REGISTRATION: ACTiVE is registered in clinicaltrials.gov (study identifier: NCT04593810 ) on 20 October 2020.

Effect of INTELLiVENT-ASV versus Conventional Ventilation on Ventilation Intensity in Patients with COVID-19 ARDS-An Observational Study.

Driving pressure (ΔP) and mechanical power (MP) are associated with outcomes in critically ill patients, irrespective of the presence of Acute Respiratory Distress Syndrome (ARDS). INTELLiVENT-ASV, a fully automated ventilatory mode, controls the settings that affect ΔP and MP. This study compared the intensity of ventilation (ΔP and MP) with INTELLiVENT-ASV versus conventional ventilation in a cohort of COVID-19 ARDS patients in two intensive care units in the Netherlands. The coprimary endpoints were ΔP and MP before and after converting from conventional ventilation to INTELLiVENT-ASV. Compared to conventional ventilation, INTELLiVENT-ASV delivered ventilation with a lower ΔP and less MP. With conventional ventilation, ΔP was 13 cmH2O, and MP was 21.5 and 24.8 J/min, whereas with INTELLiVENT-ASV, ΔP was 11 and 10 cmH2O (mean difference -2 cm H2O (95 %CI -2.5 to -1.2 cm H2O), p < 0.001) and MP was 18.8 and 17.5 J/min (mean difference -7.3 J/Min (95% CI -8.8 to -5.8 J/min), p < 0.001). Conversion from conventional ventilation to INTELLiVENT-ASV resulted in a lower intensity of ventilation. These findings may favor the use of INTELLiVENT-ASV in COVID-19 ARDS patients, but future studies remain needed to see if the reduction in the intensity of ventilation translates into clinical benefits.

Awake Proning as an Adjunctive Therapy for Refractory Hypoxemia in Non-Intubated Patients with COVID-19 Acute Respiratory Failure: Guidance from an International Group of Healthcare Workers.

Non-intubated patients with acute respiratory failure due to COVID-19 could benefit from awake proning. Awake proning is an attractive intervention in settings with limited resources, as it comes with no additional costs. However, awake proning remains poorly used probably because of unfamiliarity and uncertainties regarding potential benefits and practical application. To summarize evidence for benefit and to develop a set of pragmatic recommendations for awake proning in patients with COVID-19 pneumonia, focusing on settings where resources are limited, international healthcare professionals from high and low- and middle-income countries (LMICs) with known expertise in awake proning were invited to contribute expert advice. A growing number of observational studies describe the effects of awake proning in patients with COVID-19 pneumonia in whom hypoxemia is refractory to simple measures of supplementary oxygen. Awake proning improves oxygenation in most patients, usually within minutes, and reduces dyspnea and work of breathing. The effects are maintained for up to 1 hour after turning back to supine, and mostly disappear after 6-12 hours. In available studies, awake proning was not associated with a reduction in the rate of intubation for invasive ventilation. Awake proning comes with little complications if properly implemented and monitored. Pragmatic recommendations including indications and contraindications were formulated and adjusted for resource-limited settings. Awake proning, an adjunctive treatment for hypoxemia refractory to supplemental oxygen, seems safe in non-intubated patients with COVID-19 acute respiratory failure. We provide pragmatic recommendations including indications and contraindications for the use of awake proning in LMICs.

Comparison of Mechanical Power During Adaptive Support Ventilation Versus Nonautomated Pressure-Controlled Ventilation-A Pilot Study.

OBJECTIVES: The aim of this pilot study was to compare the amount of "mechanical power of ventilation" under adaptive support ventilation with nonautomated pressure-controlled ventilation. DESIGN: Single-center, observational prospective pilot study adjoining unitwide implementation of adaptive support ventilation in our department. SETTING: The ICU of a nonacademic teaching hospital in the Netherlands. PATIENTS: Twenty-four passive invasively ventilated critically ill patients expected to need of invasive ventilation beyond the following calendar day. MEASUREMENTS AND MAIN RESULTS: In patients under adaptive support ventilation, only positive end-expiratory pressure and Fio2 were set by the caregivers-all other ventilator settings were under control of the ventilator; in patients under pressure-controlled ventilation, maximum airway pressure (Pmax), positive end-expiratory pressure, Fio2, and respiratory rate were set by the caregivers. Mechanical power of ventilation was calculated three times per day. Compared with pressure-controlled ventilation, mechanical power of ventilation with adaptive support ventilation was lower (15.1 [10.5-25.7] vs 22.9 [18.7-28.8] J/min; p = 0.04). Tidal volume was not different, but Pmax (p = 0.012) and respiratory rate (p = 0.012) were lower with adaptive support ventilation. CONCLUSIONS: This study suggests adaptive support ventilation may have benefits compared with pressure-controlled ventilation with respect to the mechanical power of ventilation transferred from the ventilator to the respiratory system in passive invasively ventilated critically ill patients. The difference in mechanical power of ventilation is not a result of a difference in tidal volume, but the reduction in applied pressures and respiratory rate. The findings of this observational pilot study need to be confirmed in a larger, preferably randomized clinical trial.