Assessment of Inspiratory Effort in Spontaneously Breathing COVID-19 ARDS Patients Undergoing Helmet CPAP: A Comparison between Esophageal, Transdiaphragmatic and Central Venous Pressure Swing.

INTRODUCTION: The clinical features of COVID-19 are highly variable. It has been speculated that the progression across COVID-19 may be triggered by excessive inspiratory drive activation. The aim of the present study was to assess whether the tidal swing in central venous pressure (ΔCVP) is a reliable estimate of inspiratory effort. METHODS: Thirty critically ill patients with COVID-19 ARDS underwent a PEEP trial (0-5-10 cmH2O) during helmet CPAP. Esophageal (ΔPes) and transdiaphragmatic (ΔPdi) pressure swings were measured as indices of inspiratory effort. ΔCVP was assessed via a standard venous catheter. A low and a high inspiratory effort were defined as ΔPes ≤ 10 and >15 cmH2O, respectively. RESULTS: During the PEEP trial, no significant changes in ΔPes (11 [6-16] vs. 11 [7-15] vs. 12 [8-16] cmH2O, p = 0.652) and in ΔCVP (12 [7-17] vs. 11.5 [7-16] vs. 11.5 [8-15] cmH2O, p = 0.918) were detected. ΔCVP was significantly associated with ΔPes (marginal R2 0.87, p < 0.001). ΔCVP recognized both low (AUC-ROC curve 0.89 [0.84-0.96]) and high inspiratory efforts (AUC-ROC curve 0.98 [0.96-1]). CONCLUSIONS: ΔCVP is an easily available a reliable surrogate of ΔPes and can detect a low or a high inspiratory effort. This study provides a useful bedside tool to monitor the inspiratory effort of spontaneously breathing COVID-19 patients.

Geoeconomic variations in epidemiology, ventilation management, and outcomes in invasively ventilated intensive care unit patients without acute respiratory distress syndrome: a pooled analysis of four observational studies.

BACKGROUND: Geoeconomic variations in epidemiology, the practice of ventilation, and outcome in invasively ventilated intensive care unit (ICU) patients without acute respiratory distress syndrome (ARDS) remain unexplored. In this analysis we aim to address these gaps using individual patient data of four large observational studies. METHODS: In this pooled analysis we harmonised individual patient data from the ERICC, LUNG SAFE, PRoVENT, and PRoVENT-iMiC prospective observational studies, which were conducted from June, 2011, to December, 2018, in 534 ICUs in 54 countries. We used the 2016 World Bank classification to define two geoeconomic regions: middle-income countries (MICs) and high-income countries (HICs). ARDS was defined according to the Berlin criteria. Descriptive statistics were used to compare patients in MICs versus HICs. The primary outcome was the use of low tidal volume ventilation (LTVV) for the first 3 days of mechanical ventilation. Secondary outcomes were key ventilation parameters (tidal volume size, positive end-expiratory pressure, fraction of inspired oxygen, peak pressure, plateau pressure, driving pressure, and respiratory rate), patient characteristics, the risk for and actual development of acute respiratory distress syndrome after the first day of ventilation, duration of ventilation, ICU length of stay, and ICU mortality. FINDINGS: Of the 7608 patients included in the original studies, this analysis included 3852 patients without ARDS, of whom 2345 were from MICs and 1507 were from HICs. Patients in MICs were younger, shorter and with a slightly lower body-mass index, more often had diabetes and active cancer, but less often chronic obstructive pulmonary disease and heart failure than patients from HICs. Sequential organ failure assessment scores were similar in MICs and HICs. Use of LTVV in MICs and HICs was comparable (42·4% vs 44·2%; absolute difference -1·69 [-9·58 to 6·11] p=0·67; data available in 3174 [82%] of 3852 patients). The median applied positive end expiratory pressure was lower in MICs than in HICs (5 [IQR 5-8] vs 6 [5-8] cm H2O; p=0·0011). ICU mortality was higher in MICs than in HICs (30·5% vs 19·9%; p=0·0004; adjusted effect 16·41% [95% CI 9·52-23·52]; p<0·0001) and was inversely associated with gross domestic product (adjusted odds ratio for a US$10 000 increase per capita 0·80 [95% CI 0·75-0·86]; p<0·0001). INTERPRETATION: Despite similar disease severity and ventilation management, ICU mortality in patients without ARDS is higher in MICs than in HICs, with a strong association with country-level economic status. FUNDING: No funding.

Modified pediatric lung ultrasound score compared with computed tomography for assessment of lung aeration in children.

BACKGROUND: Lung ultrasound can be used to assess lung density and aeration at the bedside. Few authors have investigated scores based on the ultrasonographic interstitial syndrome for this purpose, but none have compared them with the gold standard computed tomography in children. METHODS: Children <10 kilograms undergoing a chest computed tomography for clinical purposes at a tertiary hospital Pediatric Intensive Care Unit were enrolled in the study. An ultrasound scan was performed shortly after computed tomography. Each hemithorax was divided in six zones, and each zone was scored: 1, no B lines; 2, <3 B lines; 3, >3 well separated B lines; 4, crowded, coalescent B lines; 5, white lung; 6, consolidation. The pediatric lung ultrasound score was obtained by adding all zones. Interobserver variation for two separate operators was calculated. RESULTS: Ten children, median age 95 days (range 23-721) were enrolled. Mean pediatric lung ultrasound score had a significant correlation with lung density (r=0.68) and percentage of hypoaerated lung (r=0.51). Median density and percentage of hypoaerated lung increased along the ultrasound patterns values (P<0.05) although not all patterns were significantly different from adjacent ones in the pairwise comparison. Interobserver variability in scoring of ultrasonographic patterns was moderate. CONCLUSIONS: The pediatric lung ultrasound score correlates with lung density and percentage of hypoaerated lung measured with computed tomography.

Dynamic bedside assessment of the physiologic effects of prone position in acute respiratory distress syndrome patients by electrical impedance tomography.

BACKGROUND: Prone position (PP) improves acute respiratory distress syndrome (ARDS) survival by reducing the risk of ventilation-induced lung injury. However, inter-individual variability is a hallmark of ARDS and lung protection by PP might not be optimal in all patients. In the present study, we dynamically assessed physiologic effects of PP by electrical impedance tomography (EIT) and identified predictors of improved lung protection by PP in ARDS patients. METHODS: Prospective physiologic study on 16 intubated, sedated and paralyzed patients with ARDS undergoing PP as per clinical decision. EIT data were recorded during two consecutive steps: 1) baseline supine position before and after a recruitment maneuver (RM); 2) prone position before and after a RM. "Improved lung protection" by PP was defined in the presence of simultaneous improvement of ventilation homogeneity (Hom), alveolar overdistension and collapse (ODCL) and amount of recruitable lung volume by RM in comparison to supine. RESULTS: PP versus supine increased the tidal volume distending the dependent regions (Vtdep), resulting in improved Hom (1.1±0.9 vs. 1.7±0.9, P=0.021). PP also reduced ODCL (19±9% vs. 28±8%, P=0.005) and increased the recruitable lung volume (80 [71-157] vs. 59 [1-110] mL, P=0.025). "Improved lung protection" by PP was predicted by lower Vtdep, higher Vtndep and poorer Hom measured during baseline supine position (P<0.05). CONCLUSIONS: EIT enables dynamic bedside assessment of the physiologic effects of PP and might support early recognition of ARDS patients more likely to benefit from PP.

Reliability of cutaneous landmarks for the catheter length assessment during peripherally inserted central catheter insertion: A retrospective observational study.

INTRODUCTION: Peripherally inserted central catheters are very common devices for short, medium and long-term therapies. Their performance is strictly dependent on the correct tip location, at the junction between the upper caval vein and the right atrium. It is very important to obtain an estimated measure of the catheter, in order to reach the cavo-atrial junction and optimize the catheter length. Estimated measures are often obtained using cutaneous landmarks. OBJECTIVE: Evaluate the reliability of cutaneous landmark-based length estimation during catheter insertion. Identify any patient's related factors that may affect cutaneous landmarks reliability. METHODS: We used two distinct techniques and collected data about cutaneous landmark-based length estimation, electrocardiographic guided intravascular length, age, weight and height. We studied the reliability of possible correcting factors, balancing the error average by regression models, and we found and tested two different models of prediction. RESULTS: A total number of 519 patients were studied. The average bias, between the two studied length assessment by cutaneous landmarks and electrocardiographic guided catheter length, were 3.77 ± 2.44 cm and 3.28 ± 2.57 cm, respectively. The analysed prediction models (deviance explained 43.5%, Akaike information criterion = 1313.67% and 43.4%, Akaike information criterion = 1313.92), fitted on the validation set, showed a root mean square error of 3.07 and 3.06. CONCLUSION: Landmark-based length estimation for preventive catheter length assessment seems to be unreliable, when associated with post-procedural tip location. They are useful for distal trimming catheters to optimize the 'out of skin' portion when associated with electrocardiographic tip location. Models identified for balancing bias are probably not useful.

Enteral versus intravenous approach for the sedation of critically ill patients: a randomized and controlled trial.

BACKGROUND: ICU patients must be kept conscious, calm, and cooperative even during the critical phases of illness. Enteral administration of sedative drugs might avoid over sedation, and would be as adequate as intravenous administration in patients who are awake, with fewer side effects and lower costs. This study compares two sedation strategies, for early achievement and maintenance of the target light sedation. METHODS: This was a multicenter, single-blind, randomized and controlled trial carried out in 12 Italian ICUs, involving patients with expected mechanical ventilation duration > 72 h at ICU admission and predicted mortality > 12% (Simplified Acute Physiology Score II > 32 points) during the first 24 h on ICU. Patients were randomly assigned to receive intravenous (midazolam, propofol) or enteral (hydroxyzine, lorazepam, and melatonin) sedation. The primary outcome was percentage of work shifts with the patient having an observed Richmond Agitation-Sedation Scale (RASS) = target RASS ±1. Secondary outcomes were feasibility, delirium-free and coma-free days, costs of drugs, length of ICU and hospital stay, and ICU, hospital, and one-year mortality. RESULTS: There were 348 patients enrolled. There were no differences in the primary outcome: enteral 89.8% (74.1-100), intravenous 94.4% (78-100), p = 0.20. Enteral-treated patients had more protocol violations: n = 81 (46.6%) vs 7 (4.2%), p < 0.01; more self-extubations: n = 14 (8.1%) vs 4 (2.4%), p = 0.03; a lighter sedative target (RASS = 0): 93% (71-100) vs 83% (61-100), p < 0.01; and lower total drug costs: 2.39 (0.75-9.78) vs 4.15 (1.20-20.19) €/day with mechanical ventilation (p = 0.01). CONCLUSIONS: Although enteral sedation of critically ill patients is cheaper and permits a lighter sedation target, it is not superior to intravenous sedation for reaching the RASS target. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01360346 . Registered on 25 March 2011.

Epidemiology and patterns of tracheostomy practice in patients with acute respiratory distress syndrome in ICUs across 50 countries.

BACKGROUND: To better understand the epidemiology and patterns of tracheostomy practice for patients with acute respiratory distress syndrome (ARDS), we investigated the current usage of tracheostomy in patients with ARDS recruited into the Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG-SAFE) study. METHODS: This is a secondary analysis of LUNG-SAFE, an international, multicenter, prospective cohort study of patients receiving invasive or noninvasive ventilation in 50 countries spanning 5 continents. The study was carried out over 4 weeks consecutively in the winter of 2014, and 459 ICUs participated. We evaluated the clinical characteristics, management and outcomes of patients that received tracheostomy, in the cohort of patients that developed ARDS on day 1-2 of acute hypoxemic respiratory failure, and in a subsequent propensity-matched cohort. RESULTS: Of the 2377 patients with ARDS that fulfilled the inclusion criteria, 309 (13.0%) underwent tracheostomy during their ICU stay. Patients from high-income European countries (n = 198/1263) more frequently underwent tracheostomy compared to patients from non-European high-income countries (n = 63/649) or patients from middle-income countries (n = 48/465). Only 86/309 (27.8%) underwent tracheostomy on or before day 7, while the median timing of tracheostomy was 14 (Q1-Q3, 7-21) days after onset of ARDS. In the subsample matched by propensity score, ICU and hospital stay were longer in patients with tracheostomy. While patients with tracheostomy had the highest survival probability, there was no difference in 60-day or 90-day mortality in either the patient subgroup that survived for at least 5 days in ICU, or in the propensity-matched subsample. CONCLUSIONS: Most patients that receive tracheostomy do so after the first week of critical illness. Tracheostomy may prolong patient survival but does not reduce 60-day or 90-day mortality. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02010073 . Registered on 12 December 2013.

Geo-economic variations in epidemiology, patterns of care, and outcomes in patients with acute respiratory distress syndrome: insights from the LUNG SAFE prospective cohort study.

BACKGROUND: Little information is available about the geo-economic variations in demographics, management, and outcomes of patients with acute respiratory distress syndrome (ARDS). We aimed to characterise the effect of these geo-economic variations in patients enrolled in the Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE). METHODS: LUNG SAFE was done during 4 consecutive weeks in winter, 2014, in a convenience sample of 459 intensive-care units in 50 countries across six continents. Inclusion criteria were admission to a participating intensive-care unit (including transfers) within the enrolment window and receipt of invasive or non-invasive ventilation. One of the trial's secondary aims was to characterise variations in the demographics, management, and outcome of patients with ARDS. We used the 2016 World Bank countries classification to define three major geo-economic groupings, namely European high-income countries (Europe-High), high-income countries in the rest of the world (rWORLD-High), and middle-income countries (Middle). We compared patient outcomes across these three groupings. LUNG SAFE is registered with ClinicalTrials.gov, number NCT02010073. FINDINGS: Of the 2813 patients enrolled in LUNG SAFE who fulfilled ARDS criteria on day 1 or 2, 1521 (54%) were recruited from Europe-High, 746 (27%) from rWORLD-High, and 546 (19%) from Middle countries. We noted significant geographical variations in demographics, risk factors for ARDS, and comorbid diseases. The proportion of patients with severe ARDS or with ratios of the partial pressure of arterial oxygen (PaO2) to the fractional concentration of oxygen in inspired air (FiO2) less than 150 was significantly lower in rWORLD-High countries than in the two other regions. Use of prone positioning and neuromuscular blockade was significantly more common in Europe-High countries than in the other two regions. Adjusted duration of invasive mechanical ventilation and length of stay in the intensive-care unit were significantly shorter in patients in rWORLD-High countries than in Europe-High or Middle countries. High gross national income per person was associated with increased survival in ARDS; hospital survival was significantly lower in Middle countries than in Europe-High or rWORLD-High countries. INTERPRETATION: Important geo-economic differences exist in the severity, clinician recognition, and management of ARDS, and in patients' outcomes. Income per person and outcomes in ARDS are independently associated. FUNDING: European Society of Intensive Care Medicine, St Michael's Hospital, University of Milan-Bicocca.

Neurological assessment with validated tools in general ICU: multicenter, randomized, before and after, pragmatic study to evaluate the effectiveness of an e-learning platform for continuous medical education.

BACKGROUND: International guidelines recommend systematic assessment of pain, agitation/sedation and delirium with validated scales for all ICU patients. However, these evaluations are often not done. We have created an e-learning training platform for the continuous medical education, and assessed its efficacy in increasing the use of validated tools by all medical and nursing staff of the participating ICUs during their daily practice. METHODS: Multicenter, randomized, before and after study. The eight participating centers were randomized in two groups, and received training at different times. The use of validated tools (Verbal Numeric Rating or Behavioral Pain Scale for pain; Richmond Agitation-Sedation Scale for agitation; Confusion Assessment Method for the ICU for delirium) was evaluated from clinical data recorded in medical charts during a week, with follow-up up to six months after the training. All the operators were invited to complete a questionnaire, at baseline and after the training. RESULTS: Among the 374 nurses and physicians involved, 140 (37.4%) completed at least one of the three courses. The assessment of pain (38.1 vs. 92.9%, P<0.01) and delirium (0 vs. 78.6%, P<0.01) using validated tools significantly increased after training. Observation in the follow-up showed further improvement in delirium monitoring, with no signs of extinction for pain and sedation/agitation measurements. CONCLUSIONS: This e-learning program shows encouraging effectiveness, and the increase in the use of validated tools for neurological monitoring in critically ill patients lasts over time.

Bedside assessment of the effects of positive end-expiratory pressure on lung inflation and recruitment by the helium dilution technique and electrical impedance tomography.

PURPOSE: Higher positive end-expiratory pressure might induce lung inflation and recruitment, yielding enhanced regional lung protection. We measured positive end-expiratory pressure-related lung volume changes by electrical impedance tomography and by the helium dilution technique. We also used electrical impedance tomography to assess the effects of positive end-expiratory pressure on regional determinants of ventilator-induced lung injury. METHODS: A prospective randomized crossover study was performed on 20 intubated adult patients: 12 with acute hypoxemic respiratory failure and 8 with acute respiratory distress syndrome. Each patient underwent protective controlled ventilation at lower (7 [7, 8] cmH2O) and higher (12 [12, 13] cmH2O) positive end-expiratory pressures. At the end of each phase, we collected ventilation, helium dilution, and electrical impedance tomography data. RESULTS: Positive end-expiratory pressure-induced changes in lung inflation and recruitment measured by electrical impedance tomography and helium dilution showed close correlations (R (2) = 0.78, p < 0.001 and R (2) = 0.68, p < 0.001, respectively) but with relatively variable limits of agreement. At higher positive end-expiratory pressure, recruitment was evident in all lung regions (p < 0.01) and heterogeneity of tidal ventilation distribution was reduced by increased tidal volume distending the dependent lung (p < 0.001); in the non-dependent lung, on the other hand, compliance decreased (p < 0.001) and tidal hyperinflation significantly increased (p < 0.001). In the subgroup of ARDS patients (but not in the whole study population) tidal hyperinflation in the dependent lung regions decreased at higher positive end-expiratory pressure (p = 0.05), probably indicating higher potential for recruitment. CONCLUSIONS: Close correlations exist between bedside assessment of positive end-expiratory pressure-induced changes in lung inflation and recruitment by the helium dilution and electrical impedance tomography techniques. Higher positive end-expiratory pressure exerts mixed effects on the regional determinants of ventilator-induced lung injury; these merit close monitoring.

The Ratio of Inspiratory Pressure Over Electrical Activity of the Diaphragm Remains Stable During ICU Stay and is not Related to Clinical Outcome.

BACKGROUND: We previously described an index, defined as the ratio between the inspiratory muscle pressure (Pmus) and the electrical activity of the diaphragm (EA(di)) (Pmus/EA(di) index). In the present work, we describe the trend of Pmus/EA(di) index over time, investigating whether it could be an indicator of muscular efficiency associated with risk factors for diaphragmatic injury and/or clinical outcomes. METHODS: This work is a retrospective analysis of subjects with measurements of Pmus/EA(di) index obtained, on different days, during assisted ventilation. Effects of Pmus/EA(di) index absolute value on clinical outcomes were investigated dividing subjects into those with Pmus/EA(di) index higher or lower than the median. Effects of Pmus/EA(di) index trend over time were analyzed, distinguishing between subjects with Pmus/EA(di) index increasing or decreasing. RESULTS: Mean Pmus/EA(di) index was 1.04 ± 0.67, and the median (interquartile range) was 1.00 (0.59-1.34), without a systematic trend over the days. Demographic, ventilator, or outcome data did not significantly differ between subjects with Pmus/EA(di) index higher or lower than the median. Similarly, we did not find relevant differences in subjects with Pmus/EA(di) index increasing or decreasing over time. CONCLUSIONS: The Pmus/EA(di) index value remained constant in each subject over time, although the inter-individual variability was high. Neither the Pmus/EA(di) index nor its trends appeared to be associated with ventilatory variables or clinical outcome.

Clinical assessment of auto-positive end-expiratory pressure by diaphragmatic electrical activity during pressure support and neurally adjusted ventilatory assist.

BACKGROUND: Auto-positive end-expiratory pressure (auto-PEEP) may substantially increase the inspiratory effort during assisted mechanical ventilation. Purpose of this study was to assess whether the electrical activity of the diaphragm (EAdi) signal can be reliably used to estimate auto-PEEP in patients undergoing pressure support ventilation and neurally adjusted ventilatory assist (NAVA) and whether NAVA was beneficial in comparison with pressure support ventilation in patients affected by auto-PEEP. METHODS: In 10 patients with a clinical suspicion of auto-PEEP, the authors simultaneously recorded EAdi, airway, esophageal pressure, and flow during pressure support and NAVA, whereas external PEEP was increased from 2 to 14 cm H2O. Tracings were analyzed to measure apparent "dynamic" auto-PEEP (decrease in esophageal pressure to generate inspiratory flow), auto-EAdi (EAdi value at the onset of inspiratory flow), and IDEAdi (inspiratory delay between the onset of EAdi and the inspiratory flow). RESULTS: The pressure necessary to overcome auto-PEEP, auto-EAdi, and IDEAdi was significantly lower in NAVA as compared with pressure support ventilation, decreased with increase in external PEEP, although the effect of external PEEP was less pronounced in NAVA. Both auto-EAdi and IDEAdi were tightly correlated with auto-PEEP (r = 0.94 and r = 0.75, respectively). In the presence of auto-PEEP at lower external PEEP levels, NAVA was characterized by a characteristic shape of the airway pressure. CONCLUSIONS: In patients with auto-PEEP, NAVA, compared with pressure support ventilation, led to a decrease in the pressure necessary to overcome auto-PEEP, which could be reliably monitored by the electrical activity of the diaphragm before inspiratory flow onset (auto-EAdi).

Tracheal secretion management in the mechanically ventilated patient: comparison of standard assessment and an acoustic secretion detector.

BACKGROUND: Standard indications for endotracheal suctioning are often based on clinical judgment on the deterioration of the patient's condition, and/or routine suctioning. TBA Care is a secretion detector that analyses airway sounds and indicates the need for suctioning. OBJECTIVE: To determine the efficacy of TBA Care in detecting retained secretions, compared to standard indications. METHODS: We conducted a prospective randomized trial with 72 general intensive care unit patients randomized at intubation into 2 groups, differing only in suctioning indications. The control group indications were at least 3 scheduled suctionings per day or were clinically driven. The secretion-detector group indications were device signal or clinically driven. At each suctioning session we recorded the indication for suctioning and the amount of secretions removed. Patients were followed until intensive care unit discharge or extubation. Diagnosis of ventilator-associated pneumonia was confirmed via microbiological analysis of suctioned secretions. RESULTS: We analyzed 1,705 suctionings in the control group and 1,354 in the secretion-detector group. The secretion-detector group had fewer suctionings per day (3.9 ± 2.3 vs 4.8 ± 1.2, P = .002) and a lower rate of unnecessary suctionings (4% vs 12%, P < .001). In the secretion-detector group, 97% of the suctionings were performed following the signal from the TBA Care device. In the control group, clinical deterioration (65%) was the most frequent indication for suctioning. The incidence of ventilator-associated pneumonia was similar in the groups. CONCLUSIONS: TBA Care seems to give valid and timely indications for suctioning, anticipating clinical deterioration due to secretion retention and reducing unnecessary suctionings. (ClinicalTrials.gov registration NCT00932776.).