Effect of a low versus intermediate tidal volume strategy on pulmonary complications in patients at risk of acute respiratory distress syndrome—a randomized clinical trial

IntroductionThere is no consensus on whether invasive ventilation should use low tidal volumes (VT) to prevent lung complications in patients at risk of acute respiratory distress syndrome (ARDS). The purpose of this study is to determine if a low VT strategy is more effective than an intermediate VT strategy in preventing pulmonary complications.MethodsA randomized clinical trial was conducted in invasively ventilated patients with a lung injury prediction score (LIPS) of >4 performed in the intensive care units of 10 hospitals in Spain and one in the United States of America (USA) from 3 November 2014 to 30 August 2016. Patients were randomized to invasive ventilation using low VT (≤ 6 mL/kg predicted body weight, PBW) (N = 50) or intermediate VT (> 8 mL/kg PBW) (N = 48). The primary endpoint was the development of ARDS during the first 7 days after the initiation of invasive ventilation. Secondary endpoints included the development of pneumonia and severe atelectases; the length of intensive care unit (ICU) and hospital stay; and ICU, hospital, 28– and 90–day mortality.ResultsIn total, 98 patients [67.3% male], with a median age of 65.5 years [interquartile range 55–73], were enrolled until the study was prematurely stopped because of slow recruitment and loss of equipoise caused by recent study reports. On day 7, five (11.9%) patients in the low VT group and four (9.1%) patients in the intermediate VT group had developed ARDS (risk ratio, 1.16 [95% CI, 0.62–2.17]; p = 0.735). The incidence of pneumonia and severe atelectasis was also not different between the two groups. The use of a low VT strategy did neither affect the length of ICU and hospital stay nor mortality rates.ConclusionsIn patients at risk for ARDS, a low VT strategy did not result in a lower incidence of ARDS than an intermediate VT strategy.Clinical Trial Registration: ClinicalTrials.gov, identifier NCT02070666

Protocol for a systematic review and individual patient data meta-analysis of benefit of so-called lung-protective ventilation settings in patients under general anesthesia for surgery

BACKGROUND: Almost all patients under general anesthesia for surgery need mechanical ventilation. The harmful effects of short-term intra-operative ventilation on pulmonary integrity are increasingly recognized. Recent investigations suggest protection against so-called ventilation-associated lung injury with the use of lower tidal volumes and/or the use of higher levels of positive end-expiratory pressure (PEEP). This review and meta-analysis will evaluate the effects of these protective measures on pulmonary and extra-pulmonary complications, and try to discriminate the effects of lower tidal volumes from those of higher levels of PEEP. METHODS/DESIGN: The Medline database will be searched for observational studies and randomized controlled trials of intra-operative ventilation. Individual patient data will be collected from databases obtained via direct contact with corresponding authors of original articles. The primary endpoint is development of postoperative acute respiratory distress syndrome, the most important postoperative pulmonary complication. Secondary endpoints include hospital length of stay and hospital mortality, and reported intra-operative and postoperative pulmonary and extra-pulmonary complications. Emphasis is put on separating the effects of lower tidal volumes from those of higher levels of PEEP. DISCUSSION: This will be the first meta-analysis of intra-operative ventilation using individual patient data from observational studies and randomized controlled trials. The large sample size could allow discrimination of the effect of the two most frequently used protective measures - that is, lower tidal volumes and higher levels of PEEP. The results of this review and meta-analysis can be used in designing future trials of ventilation

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

Practice of ventilation in middle-Income countries (PRoVENT-iMIC): Rationale and protocol for a prospective international multicentre observational study in intensive care units in Asia

Introduction: Current evidence on epidemiology and outcomes of invasively mechanically ventilated intensive care unit (ICU) patients is predominantly gathered in resource-rich settings. Patient casemix and patterns of critical illnesses, and probably also ventilation practices are likely to be different in resource-limited settings. We aim to investigate the epidemiological characteristics, ventilation practices and clinical outcomes of patients receiving mechanical ventilation in ICUs in Asia.Methods and Analysis: PRoVENT-iMIC (study of PRactice of VENTilation in Middle-Income Countries) is an international multicentre observational study to be undertaken in approximately 60 ICUs in 11 Asian countries. Consecutive patients aged 18 years or older who are receiving invasive ventilation in participating ICUs during a predefined 28-day period are to be enrolled, with a daily follow-up of 7 days. The primary outcome is ventilatory management (including tidal volume expressed as mL/kg predicted body weight and positive end-expiratory pressure expressed as cm H2O) during the first 3 days of mechanical ventilation-compared between patients at no risk for acute respiratory distress syndrome (ARDS), patients at risk for ARDS and in patients with ARDS (in case the diagnosis of ARDS can be made on admission). Secondary outcomes include occurrence of pulmonary complications and all-cause ICU mortality.Ethics and Dissemination: PRoVENT-iMIC will be the first international study that prospectively assesses ventilation practices, outcomes and epidemiology of invasively ventilated patients in ICUs in Asia. The results of this large study, to be disseminated through conference presentations and publications in international peer-reviewed journals, are of ultimate importance when designing trials of invasive ventilation in resource-limited ICUs. Access to source data will be made available through national or international anonymised datasets on request and after agreement of the PRoVENT-iMIC steering committee

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

Epidemiological characteristics, ventilator management, and clinical outcome in patients receiving invasive ventilation in intensive care units from 10 Asian middle-income countries (PRoVENT-iMiC): An International, multicenter, prospective study

Epidemiology, ventilator management, and outcome in patients receiving invasive ventilation in intensive care units (ICUs) in middle-income countries are largely unknown. PRactice of VENTilation in Middle-income Countries is an international multicenter 4-week observational study of invasively ventilated adult patients in 54 ICUs from 10 Asian countries conducted in 2017/18. Study outcomes included major ventilator settings (including tidal volume [V T] and positive end-expiratory pressure [PEEP]); the proportion of patients at risk for acute respiratory distress syndrome (ARDS), according to the lung injury prediction score (LIPS), or with ARDS; the incidence of pulmonary complications; and ICU mortality. In 1,315 patients included, median V T was similar in patients with LIPS \u3c 4 and patients with LIPS ≥ 4, but lower in patients with ARDS (7.90 [6.8-8.9], 8.0 [6.8-9.2], and 7.0 [5.8-8.4] mL/kg Predicted body weight; P = 0.0001). Median PEEP was similar in patients with LIPS \u3c 4 and LIPS ≥ 4, but higher in patients with ARDS (five [5-7], five [5-8], and 10 [5-12] cmH2O; P \u3c 0.0001). The proportions of patients with LIPS ≥ 4 or with ARDS were 68% (95% CI: 66-71) and 7% (95% CI: 6-8), respectively. Pulmonary complications increased stepwise from patients with LIPS \u3c 4 to patients with LIPS ≥ 4 and patients with ARDS (19%, 21%, and 38% respectively; P = 0.0002), with a similar trend in ICU mortality (17%, 34%, and 45% respectively; P \u3c 0.0001). The capacity of the LIPS to predict development of ARDS was poor (ROC AUC of 0.62, 95% CI: 0.54-0.70). In Asian middle-income countries, where two-thirds of ventilated patients are at risk for ARDS according to the LIPS and pulmonary complications are frequent, setting of V T is globally in line with current recommendations

Nebulized Heparin For Patients Under Mechanical Ventilation: An Individual Patient Data Meta-Analysis

Pulmonary coagulopathy is a characteristic feature of lung injury including ventilator-induced lung injury. The aim of this individual patient data meta-analysis is to assess the effects of nebulized anticoagulants on outcome of ventilated intensive care unit (ICU) patients. A systematic search of PubMed (1966–2014), Scopus, EMBASE, and Web of Science was conducted to identify relevant publications. Studies evaluating nebulization of anticoagulants in ventilated patients were screened for inclusion, and corresponding authors of included studies were contacted to provide individual patient data. The primary endpoint was the number of ventilator-free days and alive at day 28. Secondary endpoints included hospital mortality, ICU- and hospital-free days at day 28, and lung injury scores at day seven. We constructed a propensity score-matched cohort for comparisons between patients treated with nebulized anticoagulants and controls. Data from five studies (one randomized controlled trial, one open label study, and three studies using historical controls) were included in the meta-analysis, compassing 286 patients. In all studies unfractionated heparin was used as anticoagulant. The number of ventilator-free days and alive at day 28 was higher in patients treated with nebulized heparin compared to patients in the control group (14 [IQR 0–23] vs. 6 [IQR 0–22]), though the difference did not reach statistical significance (P = 0.459). The number of ICU-free days and alive at day 28 was significantly higher, and the lung injury scores at day seven were significantly lower in patients treated with nebulized heparin. In the propensity score-matched analysis, there were no differences in any of the endpoints. This individual patient data meta-analysis provides no convincing evidence for benefit of heparin nebulization in intubated and ventilated ICU patients. The small patient numbers and methodological shortcomings of included studies underline the need for high-quality well-powered randomized controlled trials

Associations of awake prone positioning-induced changes in physiology with intubation: An international prospective observational study in patients with acute hypoxemic respiratory failure related to COVID-19

INTRODUCTION: Awake prone positioning has the potential to improve oxygenation and decrease respiratory rate, potentially reducing the need for intubation in patients with acute hypoxemic respiratory failure. We investigated awake prone positioning-induced changes in oxygenation and respiratory rate, and the prognostic capacity for intubation in patients with COVID-19 pneumonia. METHODS: International multicenter prospective observation study in critically ill adult patients with COVID-19 receiving supplemental oxygen. We collected data on oxygenation and respiratory rate at baseline, and at 1 h after being placed in prone positioning. The combined primary outcome was oxygenation and respiratory rate at 1 h. The secondary endpoint was treatment failure, defined as need for intubation within 24 h of start of awake prone positioning. RESULTS: Between March 27th and November 2020, 101 patients were enrolled of which 99 were fully analyzable. Awake prone positioning lasted mean of 3 [2-4] h. In 77 patients (77.7%), awake prone positioning improved oxygenation, and in 37 patients (54.4%) it decreased respiratory rate. Twenty-nine patients (29.3%) were intubated within 24 h. An increase in SpO CONCLUSIONS: Awake prone positioning improves oxygenation in the majority of patients, and decreases respiratory rate in more than half of patients with acute hypoxemic respiratory failure caused by COVID-19. One in three patients need intubation within 24 h. Awake prone position-induced changes in oxygenation and respiratory rate have prognostic capacity for intubation within 24 h