Nutrition delivery across hospitalisation in critically ill patients with COVID-19: An observational study of the Australian experience.

BACKGROUND: Data on nutrition delivery over the whole hospital admission in critically ill patients with COVID-19 are scarce, particularly in the Australian setting. OBJECTIVES: The objective of this study was to describe nutrition delivery in critically ill patients admitted to Australian intensive care units (ICUs) with coronavirus disease 2019 (COVID-19), with a focus on post-ICU nutrition practices. METHODS: A multicentre observational study conducted at nine sites included adult patients with a positive COVID-19 diagnosis admitted to the ICU for >24 h and discharged to an acute ward over a 12-month recruitment period from 1 March 2020. Data were extracted on baseline characteristics and clinical outcomes. Nutrition practice data from the ICU and weekly in the post-ICU ward (up to week four) included route of feeding, presence of nutrition-impacting symptoms, and nutrition support received. RESULTS: A total of 103 patients were included (71% male, age: 58 ± 14 years, body mass index: 30±7 kg/m2), of whom 41.7% (n = 43) received mechanical ventilation within 14 days of ICU admission. While oral nutrition was received by more patients at any time point in the ICU (n = 93, 91.2% of patients) than enteral nutrition (EN) (n = 43, 42.2%) or parenteral nutrition (PN) (n = 2, 2.0%), EN was delivered for a greater duration of time (69.6% feeding days) than oral and PN (29.7% and 0.7%, respectively). More patients received oral intake than the other modes in the post-ICU ward (n = 95, 95.0%), and 40.0% (n = 38/95) of patients were receiving oral nutrition supplements. In the week after ICU discharge, 51.0% of patients (n = 51) had at least one nutrition-impacting symptom, most commonly a reduced appetite (n = 25; 24.5%) or dysphagia (n = 16; 15.7%). CONCLUSION: Critically ill patients during the COVID-19 pandemic in Australia were more likely to receive oral nutrition than artificial nutrition support at any time point both in the ICU and in the post-ICU ward, whereas EN was provided for a greater duration when it was prescribed. Nutrition-impacting symptoms were common.

COVID-19 related ICU admissions in paediatric and young adult patients in Australia: a national case series 2020–2022

Background COVID-19 pandemic research efforts have focused on disease phenotypes in adults. A distinct spectrum of illness has been documented in paediatric populations. We aimed to review paediatric intensive care unit (ICU) admissions in Australia, across differing variant predominant phases of the pandemic. Methods Data reported to the Short PeRiod IncideNce sTudy of Severe Acute Respiratory Infection (SPRINT-SARI) Australia, across 49 ICUs from February 2020 to June 2022 were extracted. We defined ‘child' as patients aged <12 years, ‘adolescent' as patients aged 12–17 years, and ‘young adult' as patients aged 18–25 years. Findings We identified 226 paediatric ICU admissions with COVID-19, representing 3.9% of ICU admissions across the study period. Comorbidity was present in 34.6% of children, 51.4% of adolescents, and 48.7% of young adults. The need for respiratory support was highest in young adults. While 28.3% of patients <18 years required invasive ventilation, in-hospital mortality in paediatric patients was 3.6%. During the Omicron period, there was an increase in the annualised incidence of age-specific COVID-19 ICU admissions per 100,000 population, albeit a decrease in the incidence per 1000 SARS-CoV-2 notifications. Interpretation This study demonstrated an appreciable burden of COVID-19 in paediatric patients. Adolescent patients presented phenotypically similar to young adults, however, illness severity was lower in younger cohorts. The Omicron phase of the pandemic demonstrated an increased age-specific population incidence of COVID-19 ICU admissions, albeit a reduced incidence when based on SARS-CoV-2 notifications. Funding SPRINT-SARI Australia is supported by the 10.13039/501100003921Department of Health, Commonwealth of Australia [Standing Deed SON60002733].

COVID-19 related ICU admissions in paediatric and young adult patients in Australia: a national case series 2020-2022.

Background: COVID-19 pandemic research efforts have focused on disease phenotypes in adults. A distinct spectrum of illness has been documented in paediatric populations. We aimed to review paediatric intensive care unit (ICU) admissions in Australia, across differing variant predominant phases of the pandemic. Methods: Data reported to the Short PeRiod IncideNce sTudy of Severe Acute Respiratory Infection (SPRINT-SARI) Australia, across 49 ICUs from February 2020 to June 2022 were extracted. We defined 'child' as patients aged <12 years, 'adolescent' as patients aged 12-17 years, and 'young adult' as patients aged 18-25 years. Findings: We identified 226 paediatric ICU admissions with COVID-19, representing 3.9% of ICU admissions across the study period. Comorbidity was present in 34.6% of children, 51.4% of adolescents, and 48.7% of young adults. The need for respiratory support was highest in young adults. While 28.3% of patients <18 years required invasive ventilation, in-hospital mortality in paediatric patients was 3.6%. During the Omicron period, there was an increase in the annualised incidence of age-specific COVID-19 ICU admissions per 100,000 population, albeit a decrease in the incidence per 1000 SARS-CoV-2 notifications. Interpretation: This study demonstrated an appreciable burden of COVID-19 in paediatric patients. Adolescent patients presented phenotypically similar to young adults, however, illness severity was lower in younger cohorts. The Omicron phase of the pandemic demonstrated an increased age-specific population incidence of COVID-19 ICU admissions, albeit a reduced incidence when based on SARS-CoV-2 notifications. Funding: SPRINT-SARI Australia is supported by the Department of Health, Commonwealth of Australia [Standing Deed SON60002733].

Long-term (180-Day) Outcomes in Critically Ill Patients With COVID-19 in the REMAP-CAP Randomized Clinical Trial.

Importance: The longer-term effects of therapies for the treatment of critically ill patients with COVID-19 are unknown. Objective: To determine the effect of multiple interventions for critically ill adults with COVID-19 on longer-term outcomes. Design, Setting, and Participants: Prespecified secondary analysis of an ongoing adaptive platform trial (REMAP-CAP) testing interventions within multiple therapeutic domains in which 4869 critically ill adult patients with COVID-19 were enrolled between March 9, 2020, and June 22, 2021, from 197 sites in 14 countries. The final 180-day follow-up was completed on March 2, 2022. Interventions: Patients were randomized to receive 1 or more interventions within 6 treatment domains: immune modulators (n = 2274), convalescent plasma (n = 2011), antiplatelet therapy (n = 1557), anticoagulation (n = 1033), antivirals (n = 726), and corticosteroids (n = 401). Main Outcomes and Measures: The main outcome was survival through day 180, analyzed using a bayesian piecewise exponential model. A hazard ratio (HR) less than 1 represented improved survival (superiority), while an HR greater than 1 represented worsened survival (harm); futility was represented by a relative improvement less than 20% in outcome, shown by an HR greater than 0.83. Results: Among 4869 randomized patients (mean age, 59.3 years; 1537 [32.1%] women), 4107 (84.3%) had known vital status and 2590 (63.1%) were alive at day 180. IL-6 receptor antagonists had a greater than 99.9% probability of improving 6-month survival (adjusted HR, 0.74 [95% credible interval {CrI}, 0.61-0.90]) and antiplatelet agents had a 95% probability of improving 6-month survival (adjusted HR, 0.85 [95% CrI, 0.71-1.03]) compared with the control, while the probability of trial-defined statistical futility (HR >0.83) was high for therapeutic anticoagulation (99.9%; HR, 1.13 [95% CrI, 0.93-1.42]), convalescent plasma (99.2%; HR, 0.99 [95% CrI, 0.86-1.14]), and lopinavir-ritonavir (96.6%; HR, 1.06 [95% CrI, 0.82-1.38]) and the probabilities of harm from hydroxychloroquine (96.9%; HR, 1.51 [95% CrI, 0.98-2.29]) and the combination of lopinavir-ritonavir and hydroxychloroquine (96.8%; HR, 1.61 [95% CrI, 0.97-2.67]) were high. The corticosteroid domain was stopped early prior to reaching a predefined statistical trigger; there was a 57.1% to 61.6% probability of improving 6-month survival across varying hydrocortisone dosing strategies. Conclusions and Relevance: Among critically ill patients with COVID-19 randomized to receive 1 or more therapeutic interventions, treatment with an IL-6 receptor antagonist had a greater than 99.9% probability of improved 180-day mortality compared with patients randomized to the control, and treatment with an antiplatelet had a 95.0% probability of improved 180-day mortality compared with patients randomized to the control. Overall, when considered with previously reported short-term results, the findings indicate that initial in-hospital treatment effects were consistent for most therapies through 6 months.

Prognostication using SpO2/FiO2 in invasively ventilated ICU patients with ARDS due to COVID-19 - Insights from the PRoVENT-COVID study.

BACKGROUND: The SpO2/FiO2 is a useful oxygenation parameter with prognostic capacity in patients with ARDS. We investigated the prognostic capacity of SpO2/FiO2 for mortality in patients with ARDS due to COVID-19. METHODS: This was a post-hoc analysis of a national multicenter cohort study in invasively ventilated patients with ARDS due to COVID-19. The primary endpoint was 28-day mortality. RESULTS: In 869 invasively ventilated patients, 28-day mortality was 30.1%. The SpO2/FiO2 on day 1 had no prognostic value. The SpO2/FiO2 on day 2 and day 3 had prognostic capacity for death, with the best cut-offs being 179 and 199, respectively. Both SpO2/FiO2 on day 2 (OR, 0.66 [95%-CI 0.46-0.96]) and on day 3 (OR, 0.70 [95%-CI 0.51-0.96]) were associated with 28-day mortality in a model corrected for age, pH, lactate levels and kidney dysfunction (AUROC 0.78 [0.76-0.79]). The measured PaO2/FiO2 and the PaO2/FiO2 calculated from SpO2/FiO2 were strongly correlated (Spearman's r = 0.79). CONCLUSIONS: In this cohort of patients with ARDS due to COVID-19, the SpO2/FiO2 on day 2 and day 3 are independently associated with and have prognostic capacity for 28-day mortality. The SpO2/FiO2 is a useful metric for risk stratification in invasively ventilated COVID-19 patients.

Longitudinal respiratory subphenotypes in patients with COVID-19-related acute respiratory distress syndrome: results from three observational cohorts.

BACKGROUND: Patients with COVID-19-related acute respiratory distress syndrome (ARDS) have been postulated to present with distinct respiratory subphenotypes. However, most phenotyping schema have been limited by sample size, disregard for temporal dynamics, and insufficient validation. We aimed to identify respiratory subphenotypes of COVID-19-related ARDS using unbiased data-driven approaches. METHODS: PRoVENT-COVID was an investigator-initiated, national, multicentre, prospective, observational cohort study at 22 intensive care units (ICUs) in the Netherlands. Consecutive patients who had received invasive mechanical ventilation for COVID-19 (aged 18 years or older) served as the derivation cohort, and similar patients from two ICUs in the USA served as the replication cohorts. COVID-19 was confirmed by positive RT-PCR. We used latent class analysis to identify subphenotypes using clinically available respiratory data cross-sectionally at baseline, and longitudinally using 8-hourly data from the first 4 days of invasive ventilation. We used group-based trajectory modelling to evaluate trajectories of individual variables and to facilitate potential clinical translation. The PRoVENT-COVID study is registered with ClinicalTrials.gov, NCT04346342. FINDINGS: Between March 1, 2020, and May 15, 2020, 1007 patients were admitted to participating ICUs in the Netherlands, and included in the derivation cohort. Data for 288 patients were included in replication cohort 1 and 326 in replication cohort 2. Cross-sectional latent class analysis did not identify any underlying subphenotypes. Longitudinal latent class analysis identified two distinct subphenotypes. Subphenotype 2 was characterised by higher mechanical power, minute ventilation, and ventilatory ratio over the first 4 days of invasive mechanical ventilation than subphenotype 1, but PaO2/FiO2, pH, and compliance of the respiratory system did not differ between the two subphenotypes. 185 (28%) of 671 patients with subphenotype 1 and 109 (32%) of 336 patients with subphenotype 2 had died at day 28 (p=0·10). However, patients with subphenotype 2 had fewer ventilator-free days at day 28 (median 0, IQR 0-15 vs 5, 0-17; p=0·016) and more frequent venous thrombotic events (109 [32%] of 336 patients vs 176 [26%] of 671 patients; p=0·048) compared with subphenotype 1. Group-based trajectory modelling revealed trajectories of ventilatory ratio and mechanical power with similar dynamics to those observed in latent class analysis-derived trajectory subphenotypes. The two trajectories were: a stable value for ventilatory ratio or mechanical power over the first 4 days of invasive mechanical ventilation (trajectory A) or an upward trajectory (trajectory B). However, upward trajectories were better independent prognosticators for 28-day mortality (OR 1·64, 95% CI 1·17-2·29 for ventilatory ratio; 1·82, 1·24-2·66 for mechanical power). The association between upward ventilatory ratio trajectories (trajectory B) and 28-day mortality was confirmed in the replication cohorts (OR 4·65, 95% CI 1·87-11·6 for ventilatory ratio in replication cohort 1; 1·89, 1·05-3·37 for ventilatory ratio in replication cohort 2). INTERPRETATION: At baseline, COVID-19-related ARDS has no consistent respiratory subphenotype. Patients diverged from a fairly homogenous to a more heterogeneous population, with trajectories of ventilatory ratio and mechanical power being the most discriminatory. Modelling these parameters alone provided prognostic value for duration of mechanical ventilation and mortality. FUNDING: Amsterdam UMC.

Association of Positive End-Expiratory Pressure and Lung Recruitment Selection Strategies with Mortality in Acute Respiratory Distress Syndrome: A Systematic Review and Network Meta-analysis.

Rationale: The most beneficial positive end-expiratory pressure (PEEP) selection strategy in patients with acute respiratory distress syndrome (ARDS) is unknown, and current practice is variable. Objectives: To compare the relative effects of different PEEP selection strategies on mortality in adults with moderate to severe ARDS. Methods: We conducted a network meta-analysis using a Bayesian framework. Certainty of evidence was evaluated using grading of recommendations assessment, development and evaluation methodology. Measurements and Main Results: We included 18 randomized trials (4,646 participants). Compared with a lower PEEP strategy, the posterior probability of mortality benefit from a higher PEEP without lung recruitment maneuver (LRM) strategy was 99% (risk ratio [RR], 0.77; 95% credible interval [CrI], 0.60-0.96, high certainty), the posterior probability of benefit of the esophageal pressure-guided strategy was 87% (RR, 0.77; 95% CrI, 0.48-1.22, moderate certainty), the posterior probability of benefit of a higher PEEP with brief LRM strategy was 96% (RR, 0.83; 95% CrI, 0.67-1.02, moderate certainty), and the posterior probability of increased mortality from a higher PEEP with prolonged LRM strategy was 77% (RR, 1.06; 95% CrI, 0.89-1.22, low certainty). Compared with a higher PEEP without LRM strategy, the posterior probability of increased mortality from a higher PEEP with prolonged LRM strategy was 99% (RR, 1.37; 95% CrI, 1.04-1.81, moderate certainty). Conclusions: In patients with moderate to severe ARDS, higher PEEP without LRM is associated with a lower risk of death than lower PEEP. A higher PEEP with prolonged LRM strategy is associated with increased risk of death when compared with higher PEEP without LRM.

Analysis of mobility level of COVID-19 patients undergoing mechanical ventilation support: A single center, retrospective cohort study.

BACKGROUND: Severe coronavirus disease 2019 (COVID-19) patients frequently require mechanical ventilation (MV) and undergo prolonged periods of bed rest with restriction of activities during the intensive care unit (ICU) stay. Our aim was to address the degree of mobilization in critically ill patients with COVID-19 undergoing to MV support. METHODS: Retrospective single-center cohort study. We analyzed patients' mobility level, through the Perme ICU Mobility Score (Perme Score) of COVID-19 patients admitted to the ICU. The Perme Mobility Index (PMI) was calculated [PMI = ΔPerme Score (ICU discharge-ICU admission)/ICU length of stay], and patients were categorized as "improved" (PMI > 0) or "not improved" (PMI ≤ 0). Comparisons were performed with stratification according to the use of MV support. RESULTS: From February 2020, to February 2021, 1,297 patients with COVID-19 were admitted to the ICU and assessed for eligibility. Out of those, 949 patients were included in the study [524 (55.2%) were classified as "improved" and 425 (44.8%) as "not improved"], and 396 (41.7%) received MV during ICU stay. The overall rate of patients out of bed and able to walk ≥ 30 meters at ICU discharge were, respectively, 526 (63.3%) and 170 (20.5%). After adjusting for confounders, independent predictors of improvement of mobility level were frailty (OR: 0.52; 95% CI: 0.29-0.94; p = 0.03); SAPS III Score (OR: 0.75; 95% CI: 0.57-0.99; p = 0.04); SOFA Score (OR: 0.58; 95% CI: 0.43-0.78; p < 0.001); use of MV after the first hour of ICU admission (OR: 0.41; 95% CI: 0.17-0.99; p = 0.04); tracheostomy (OR: 0.54; 95% CI: 0.30-0.95; p = 0.03); use of extracorporeal membrane oxygenation (OR: 0.21; 95% CI: 0.05-0.8; p = 0.03); neuromuscular blockade (OR: 0.53; 95% CI: 0.3-0.95; p = 0.03); a higher Perme Score at admission (OR: 0.35; 95% CI: 0.28-0.43; p < 0.001); palliative care (OR: 0.05; 95% CI: 0.01-0.16; p < 0.001); and a longer ICU stay (OR: 0.79; 95% CI: 0.61-0.97; p = 0.04) were associated with a lower chance of mobility improvement, while non-invasive ventilation within the first hour of ICU admission and after the first hour of ICU admission (OR: 2.45; 95% CI: 1.59-3.81; p < 0.001) and (OR: 2.25; 95% CI: 1.56-3.26; p < 0.001), respectively; and vasopressor use (OR: 2.39; 95% CI: 1.07-5.5; p = 0.03) were associated with a higher chance of mobility improvement. CONCLUSION: The use of MV reduced mobility status in less than half of critically ill COVID-19 patients.

Angiotensin II infusion in COVID-19: An international, multicenter, registry-based study.

To expand our understanding of the role of angiotensin II (ANGII) in coronavirus infectious disease 2019 (COVID-19), we conducted an international, multicenter registry study to assess the use of ANGII in patients with COVID-19 compared to patients not receiving ANGII. Critically ill adult patients who were diagnosed with COVID-19 and received ANGII were matched with COVID-19 patients not receiving ANGII according to age, respiratory support, history of hypertension, use of angiotensin-converting enzyme inhibitors and/or ANGII receptor blocker, and date of admission. All outcomes were exploratory in nature and included improvement in oxygenation, duration of organ support, and mortality. In one year, 132 patients were included (65 in the ANGII group and 67 in the control group), and patients were comparable in baseline characteristics. During the first 12 h of infusion, patients in the ANGII had a faster decrease in FiO2  and maintained similar mean arterial pressure levels. Hospital mortality was not statistically significantly different between the groups (53.8% vs. 40.3%; p = 0.226). Within the limitations of such a study design, our findings confirm previous observations of a potentially positive effect of ANGII on blood pressure and FiO2 but no effect on patient-centered outcomes.

Association of early positive end-expiratory pressure settings with ventilator-free days in patients with coronavirus disease 2019 acute respiratory distress syndrome: A secondary analysis of the Practice of VENTilation in COVID-19 study.

BACKGROUND: There is uncertainty about how much positive end-expiratory pressure (PEEP) should be used in patients with acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19). OBJECTIVE: To investigate whether a higher PEEP strategy is superior to a lower PEEP strategy regarding the number of ventilator-free days (VFDs). DESIGN: Multicentre observational study conducted from 1 March to 1 June 2020. SETTING AND PATIENTS: Twenty-two ICUs in The Netherlands and 933 invasively ventilated COVID-19 ARDS patients. INTERVENTIONS: Patients were categorised retrospectively as having received invasive ventilation with higher (n=259) or lower PEEP (n=674), based on the high and low PEEP/FiO2 tables of the ARDS Network, and using ventilator settings and parameters in the first hour of invasive ventilation, and every 8 h thereafter at fixed time points during the first four calendar days. We also used propensity score matching to control for observed confounding factors that might influence outcomes. MAIN OUTCOMES AND MEASURES: The primary outcome was the number of VFDs. Secondary outcomes included distant organ failures including acute kidney injury (AKI) and use of renal replacement therapy (RRT), and mortality. RESULTS: In the unmatched cohort, the higher PEEP strategy had no association with the median [IQR] number of VFDs (2.0 [0.0 to 15.0] vs. 0.0 [0.0 to 16.0] days). The median (95% confidence interval) difference was 0.21 (-3.34 to 3.78) days, P = 0.905. In the matched cohort, the higher PEEP group had an association with a lower median number of VFDs (0.0 [0.0 to 14.0] vs. 6.0 [0.0 to 17.0] days) a median difference of -4.65 (-8.92 to -0.39) days, P = 0.032. The higher PEEP strategy had associations with higher incidence of AKI (in the matched cohort) and more use of RRT (in the unmatched and matched cohorts). The higher PEEP strategy had no association with mortality. CONCLUSION: In COVID-19 ARDS, use of higher PEEP may be associated with a lower number of VFDs, and may increase the incidence of AKI and need for RRT. TRIAL REGISTRATION: Practice of VENTilation in COVID-19 is registered at ClinicalTrials.gov, NCT04346342.

Prognostication using SpO2/FiO2 in invasively ventilated ICU patients with ARDS due to COVID-19 – Insights from the PRoVENT-COVID study☆

Background The SpO2/FiO2 is a useful oxygenation parameter with prognostic capacity in patients with ARDS. We investigated the prognostic capacity of SpO2/FiO2 for mortality in patients with ARDS due to COVID–19. Methods This was a post-hoc analysis of a national multicenter cohort study in invasively ventilated patients with ARDS due to COVID–19. The primary endpoint was 28–day mortality. Results In 869 invasively ventilated patients, 28–day mortality was 30.1%. The SpO2/FiO2 on day 1 had no prognostic value. The SpO2/FiO2 on day 2 and day 3 had prognostic capacity for death, with the best cut-offs being 179 and 199, respectively. Both SpO2/FiO2 on day 2 (OR, 0.66 [95%–CI 0.46–0.96]) and on day 3 (OR, 0.70 [95%–CI 0.51–0.96]) were associated with 28–day mortality in a model corrected for age, pH, lactate levels and kidney dysfunction (AUROC 0.78 [0.76–0.79]). The measured PaO2/FiO2 and the PaO2/FiO2 calculated from SpO2/FiO2 were strongly correlated (Spearman's r = 0.79). Conclusions In this cohort of patients with ARDS due to COVID–19, the SpO2/FiO2 on day 2 and day 3 are independently associated with and have prognostic capacity for 28–day mortality. The SpO2/FiO2 is a useful metric for risk stratification in invasively ventilated COVID–19 patients.

Association of Time-Varying Intensity of Ventilation With Mortality in Patients With COVID-19 ARDS: Secondary Analysis of the PRoVENT-COVID Study.

Background: High intensity of ventilation has an association with mortality in patients with acute respiratory failure. It is uncertain whether similar associations exist in patients with acute respiratory distress syndrome (ARDS) patients due to coronavirus disease 2019 (COVID-19). We investigated the association of exposure to different levels of driving pressure (ΔP) and mechanical power (MP) with mortality in these patients. Methods: PRoVENT-COVID is a national, retrospective observational study, performed at 22 ICUs in the Netherlands, including COVID-19 patients under invasive ventilation for ARDS. Dynamic ΔP and MP were calculated at fixed time points during the first 4 calendar days of ventilation. The primary endpoint was 28-day mortality. To assess the effects of time-varying exposure, Bayesian joint models adjusted for confounders were used. Results: Of 1,122 patients included in the PRoVENT-COVID study, 734 were eligible for this analysis. In the first 28 days, 29.2% of patients died. A significant increase in the hazard of death was found to be associated with each increment in ΔP (HR 1.04, 95% CrI 1.01-1.07) and in MP (HR 1.12, 95% CrI 1.01-1.36). In sensitivity analyses, cumulative exposure to higher levels of ΔP or MP resulted in increased risks for 28-day mortality. Conclusion: Cumulative exposure to higher intensities of ventilation in COVID-19 patients with ARDS have an association with increased risk of 28-day mortality. Limiting exposure to high ΔP or MP has the potential to improve survival in these patients. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT04346342.

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.

Incidence and Practice of Early Prone Positioning in Invasively Ventilated COVID-19 Patients-Insights from the PRoVENT-COVID Observational Study.

We describe the incidence and practice of prone positioning and determined the association of use of prone positioning with outcomes in invasively ventilated patients with acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19) in a national, multicenter observational study, performed at 22 intensive care units in the Netherlands. Patients were categorized into 4 groups, based on indication for and actual use of prone positioning. The primary outcome was 28-day mortality. Secondary endpoints were 90-day mortality, and ICU and hospital length of stay. In 734 patients, prone positioning was indicated in 60%-the incidence of prone positioning was higher in patients with an indication than in patients without an indication for prone positioning (77 vs. 48%, p = 0.001). Patients were left in the prone position for median 15.0 (10.5-21.0) hours per full calendar day-the duration was longer in patients with an indication than in patients without an indication for prone positioning (16.0 (11.0-23.0) vs. 14.0 (10.0-19.0) hours, p < 0.001). Ventilator settings and ventilation parameters were not different between the four groups, except for FiO2 which was higher in patients having an indication for and actually receiving prone positioning. Our data showed no difference in mortality at day 28 between the 4 groups (HR no indication, no prone vs. no indication, prone vs. indication, no prone vs. indication, prone: 1.05 (0.76-1.45) vs. 0.88 (0.62-1.26) vs. 1.15 (0.80-1.54) vs. 0.96 (0.73-1.26) (p = 0.08)). Factors associated with the use of prone positioning were ARDS severity and FiO2. The findings of this study are that prone positioning is often used in COVID-19 patients, even in patients that have no indication for this intervention. Sessions of prone positioning lasted long. Use of prone positioning may affect outcomes.

Association of intensity of ventilation with 28-day mortality in COVID-19 patients with acute respiratory failure: insights from the PRoVENT-COVID study.

BACKGROUND: The intensity of ventilation, reflected by driving pressure (ΔP) and mechanical power (MP), has an association with outcome in invasively ventilated patients with or without acute respiratory distress syndrome (ARDS). It is uncertain if a similar association exists in coronavirus disease 2019 (COVID-19) patients with acute respiratory failure. METHODS: We aimed to investigate the impact of intensity of ventilation on patient outcome. The PRoVENT-COVID study is a national multicenter observational study in COVID-19 patients receiving invasive ventilation. Ventilator parameters were collected a fixed time points on the first calendar day of invasive ventilation. Mean dynamic ΔP and MP were calculated for individual patients at time points without evidence of spontaneous breathing. A Cox proportional hazard model, and a double stratification analysis adjusted for confounders were used to estimate the independent associations of ΔP and MP with outcome. The primary endpoint was 28-day mortality. RESULTS: In 825 patients included in this analysis, 28-day mortality was 27.5%. ΔP was not independently associated with mortality (HR 1.02 [95% confidence interval 0.88-1.18]; P = 0.750). MP, however, was independently associated with 28-day mortality (HR 1.17 [95% CI 1.01-1.36]; P = 0.031), and increasing quartiles of MP, stratified on comparable levels of ΔP, had higher risks of 28-day mortality (HR 1.15 [95% CI 1.01-1.30]; P = 0.028). CONCLUSIONS: In this cohort of critically ill invasively ventilated COVID-19 patients with acute respiratory failure, we show an independent association of MP, but not ΔP with 28-day mortality. MP could serve as one prognostic biomarker in addition to ΔP in these patients. Efforts aiming at limiting both ΔP and MP could translate in a better outcome. Trial registration Clinicaltrials.gov (study identifier NCT04346342).

TELE-critical Care verSus usual Care On ICU PErformance (TELESCOPE): protocol for a cluster-randomised clinical trial on adult general ICUs in Brazil.

INTRODUCTION: Daily multidisciplinary rounds (DMRs) consist of systematic patient-centred discussions aiming to establish joint therapeutic goals for the next 24 hours of intensive care unit (ICU) care. The aim of the present study protocol is to evaluate whether an intervention consisting of guided DMRs, supported by a remote specialist and audit/feedback on care performance will reduce ICU length of stay compared with a control group. METHODS AND ANALYSIS: A multicentre, controlled, cluster-randomised superiority trial including 30 ICUs in Brazil (15 intervention and 15 control), from August 2019 to June 2021. In a parallel assignment, ICUs are randomised to a complex-intervention composed by daily rounds carried out through Tele-ICU by a remote ICU physician; development of local quality indicators dashboards coupled with monthly meetings with local leadership; and dissemination of evidence-based clinical protocols versus usual care. Primary outcome is ICU length of stay. Secondary outcomes include classification of the unit according to the profiles defined by the standardised resource use and the standardised mortality rate, hospital mortality, incidence of healthcare-associated infections, ventilator-free days at 28 days, patient-days receiving oral or enteral feeding, patient-days under light sedation or alert and calm, rate of patients under normoxaemia. All adult patients admitted after the beginning of the study in each participant ICU will be enrolled. Inclusion criteria (clusters): public Brazilian ICUs with a minimum of 8 ICU beds interested/committed to participating in the study. Exclusion criteria (clusters): units with fully established DMRs by an intensivist, specialised or step-down units. ETHICS AND DISSEMINATION: The study protocol was approved by the institutional review board (IRB) of the coordinator centre, and by IRBs of each enrolled hospital/ICU. Statistical analysis protocol is being prepared for submission before the end of patient's enrolment. Results will be disseminated through conferences, peer-reviewed journals and to each participating unit. TRIAL REGISTRATION NUMBER: NCT03920501; Pre-results.

Immunosuppressive strategies in invasively ventilated ARDS COVID-19 patients.

BACKGROUND: COVID-19 is associated with elevated levels of inflammatory cytokines. We present the characteristics and outcomes of patients treated in the Intensive Care Unit (ICU) with immunosuppressive drugs, either tocilizumab or anakinra compared with controls. METHODS: A single-center observational prospective study on ICU invasively ventilated COVID-19 patients. The primary outcome was the clinical improvement at day 28. A Bayesian framework was employed, and all analyses were adjusted for confounders. RESULTS: Sixty-one consecutive invasively ventilated patients were included, nine (14.7%) received tocilizumab and 15 (24.6%) received anakinra. Over the first seven days, tocilizumab was associated with a greater decrease in C-reactive protein (P<0.001). After adjusting for confounders, the probability of clinical improvement at day 28 compared to control was 7∙6% (OR=0.36 [95% CrI: 0.09-1.46]) for tocilizumab and 40.9% (OR=0.89 [95% CrI: 0.32-2.43]) for anakinra. At day 28, the probability of being in a better clinical category was 2.5% (OR=2.98 [95% CrI: 1.00-8.88]) for tocilizumab, and 49.5% (OR=1.00 [95% CrI: 0.42-2.42]) for anakinra. CONCLUSIONS: In invasively ventilated COVID-19 patients, treatment with anakinra was associated with a higher probability of clinical improvement compared to tocilizumab; however, treatment with either drug did not result in clinically meaningful improvements compared with controls.

The Perme Mobility Index: A new concept to assess mobility level in patients with coronavirus (COVID-19) infection.

INTRODUCTION: The Coronavirus Disease 2019 (COVID-19) outbreak is evolving rapidly worldwide. Data on the mobility level of patients with COVID-19 in the intensive care unit (ICU) are needed. OBJECTIVE: To describe the mobility level of patients with COVID-19 admitted to the ICU and to address factors associated with mobility level at the time of ICU discharge. METHODS: Single center, retrospective cohort study. Consecutive patients admitted to the ICU with confirmed COVID-19 infection were analyzed. The mobility status was assessed by the Perme Score at admission and discharge from ICU with higher scores indicating higher mobility level. The Perme Mobility Index (PMI) was calculated [PMI = ΔPerme Score (ICU discharge-ICU admission)/ICU length of stay]. Based on the PMI, patients were divided into two groups: "Improved" (PMI > 0) and "Not improved" (PMI ≤ 0). RESULTS: A total of 136 patients were included in this analysis. The hospital mortality rate was 16.2%. The Perme Score improved significantly when comparing ICU discharge with ICU admission [20.0 (7-28) points versus 7.0 (0-16) points; P < 0.001]. A total of 88 patients (64.7%) improved their mobility level during ICU stay, and the median PMI of these patients was 1.5 (0.6-3.4). Patients in the improved group had a lower duration of mechanical ventilation [10 (5-14) days versus 15 (8-24) days; P = 0.021], lower hospital length of stay [25 (12-37) days versus 30 (11-48) days; P < 0.001], and lower ICU and hospital mortality rate. Independent predictors for mobility level were lower age, lower Charlson Comorbidity Index, and not having received renal replacement therapy. CONCLUSION: Patients' mobility level was low at ICU admission; however, most patients improved their mobility level during ICU stay. Risk factors associated with the mobility level were age, comorbidities, and use of renal replacement therapy.

Ventilation management in acute respiratory failure related to COVID-19 versus ARDS from another origin - a descriptive narrative review.

INTRODUCTION: It is uncertain whether ventilation in patients with acute respiratory failure related to coronavirus disease 2019 (COVID-19) differs from that in patients with acute respiratory distress syndrome (ARDS) from another origin. AREAS COVERED: We undertook two literature searches in PubMed to identify observational studies reporting on ventilation management--one in patients with acute respiratory failure related to COVID-19, and one in patients with ARDS from another origin. The searches identified 14 studies in patients with acute respiratory failure related to COVID-19, and 8 studies in patients with ARDS from another origin. EXPERT OPINION: In patients with acute respiratory failure related to COVID-19, ventilation management seems to be similar to that of patients with ARDS from another origin. The future lies in studies focused on personalized treatment of ARDS of all origins, including COVID-19.

Associations of Body Mass Index with Ventilation Management and Clinical Outcomes in Invasively Ventilated Patients with ARDS Related to COVID-19-Insights from the PRoVENT-COVID Study.

We describe the practice of ventilation and mortality rates in invasively ventilated normal-weight (18.5 ≤ BMI ≤ 24.9 kg/m2), overweight (25.0 ≤ BMI ≤ 29.9 kg/m2), and obese (BMI > 30 kg/m2) COVID-19 ARDS patients in a national, multicenter observational study, performed at 22 intensive care units in the Netherlands. The primary outcome was a combination of ventilation variables and parameters over the first four calendar days of ventilation, including tidal volume, positive end-expiratory pressure (PEEP), respiratory system compliance, and driving pressure in normal-weight, overweight, and obese patients. Secondary outcomes included the use of adjunctive treatments for refractory hypoxaemia and mortality rates. Between 1 March 2020 and 1 June 2020, 1122 patients were included in the study: 244 (21.3%) normal-weight patients, 531 (47.3%) overweight patients, and 324 (28.8%) obese patients. Most patients received a tidal volume < 8 mL/kg PBW; only on the first day was the tidal volume higher in obese patients. PEEP and driving pressure were higher, and compliance of the respiratory system was lower in obese patients on all four days. Adjunctive therapies for refractory hypoxemia were used equally in the three BMI groups. Adjusted mortality rates were not different between BMI categories. The findings of this study suggest that lung-protective ventilation with a lower tidal volume and prone positioning is similarly feasible in normal-weight, overweight, and obese patients with ARDS related to COVID-19. A patient's BMI should not be used in decisions to forgo or proceed with invasive ventilation.