The weaning from mechanical ventilation: a comprehensive ultrasound approach.

PURPOSE OF REVIEW: Due to heart, lung and diaphragm interactions during weaning from mechanical ventilation, an ultrasound integrated approach may be useful in the detection of dysfunctions potentially leading to weaning failure. In this review, we will summarize the most recent advances concerning the ultrasound applications relevant to the weaning from mechanical ventilation. RECENT FINDINGS: The role of ultrasonographic examination of heart, lung and diaphragm has been deeply investigated over the years. Most recent findings concern the ability of lung ultrasound in detecting weaning induced pulmonary edema during spontaneous breathing trial. Furthermore, in patients at high risk of cardiac impairments, global and anterolateral lung ultrasound scores have been correlated with weaning and extubation failure, whereas echocardiographic indexes were not. For diaphragmatic ultrasound evaluation, new indexes have been proposed for the evaluation of diaphragm performance during weaning, but further studies are needed to validate these results. SUMMARY: The present review summarizes the potential role of ultrasonography in the weaning process. A multimodal integrated approach allows the clinician to comprehend the pathophysiological processes of weaning failure.

Effects of Varying Levels of Inspiratory Assistance with Pressure Support Ventilation and Neurally Adjusted Ventilatory Assist on Driving Pressure in Patients Recovering from Hypoxemic Respiratory Failure.

BACKGROUND: Driving pressure can be readily measured during assisted modes of ventilation such as pressure support ventilation (PSV) and neurally adjusted ventilatory assist (NAVA). The present prospective randomized crossover study aimed to assess the changes in driving pressure in response to variations in the level of assistance delivered by PSV vs NAVA. METHODS: 16 intubated adult patients, recovering from hypoxemic acute respiratory failure (ARF) and undergoing assisted ventilation, were randomly subjected to six 30-min-lasting trials. At baseline, PSV (PSV100) was set with the same regulation present at patient enrollment. The corresponding level of NAVA (NAVA100) was set to match the same inspiratory peak of airway pressure obtained in PSV100. Therefore, the level of assistance was reduced and increased by 50% in both ventilatory modes (PSV50, NAVA50; PSV150, NAVA150). At the end of each trial, driving pressure obtained in response to four short (2-3 s) end-expiratory and end-inspiratory occlusions was analyzed. RESULTS: Driving pressure at PSV50 (6.6 [6.1-7.8] cmH2O) was lower than that recorded at PSV100 (7.9 [7.2-9.1] cmH2O, P = 0.005) and PSV150 (9.9 [9.1-13.2] cmH2O, P < 0.0001). In NAVA, driving pressure at NAVA50 was reduced compared to NAVA150 (7.7 [5.1-8.1] cmH2O vs 8.3 [6.4-11.4] cmH2O, P = 0.013), whereas there were no changes between baseline and NAVA150 (8.5 [6.3-9.8] cmH2O vs 8.3 [6.4-11.4] cmH2O, P = 0.331, respectively). Driving pressure at PSV150 was higher than that observed in NAVA150 (P = 0.011). CONCLUSIONS: NAVA delivers better lung-protective ventilation compared to PSV in hypoxemic ARF patients. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION: The present trial was prospectively registered at www.clinicatrials.gov (NCT03719365) on 24 October 2018.

Vasopressor-Sparing Strategies in Patients with Shock: A Scoping-Review and an Evidence-Based Strategy Proposition.

Despite the abundant literature on vasopressor therapy, few studies have focused on vasopressor-sparing strategies in patients with shock. We performed a scoping-review of the published studies evaluating vasopressor-sparing strategies by analyzing the results from randomized controlled trials conducted in patients with shock, with a focus on vasopressor doses and/or duration reduction. We analyzed 143 studies, mainly performed in septic shock. Our analysis demonstrated that several pharmacological and non-pharmacological strategies are associated with a decrease in the duration of vasopressor therapy. These strategies are as follows: implementing a weaning strategy, vasopressin use, systemic glucocorticoid administration, beta-blockers, and normothermia. On the contrary, early goal directed therapies, including fluid therapy, oral vasopressors, vitamin C, and renal replacement therapy, are not associated with an increase in vasopressor-free days. Based on these results, we proposed an evidence-based vasopressor management strategy.

Early extubation with immediate non-invasive ventilation versus standard weaning in intubated patients for coronavirus disease 2019: a retrospective multicenter study.

In patients intubated for hypoxemic acute respiratory failure (ARF) related to novel coronavirus disease (COVID-19), we retrospectively compared two weaning strategies, early extubation with immediate non-invasive ventilation (NIV) versus standard weaning encompassing spontaneous breathing trial (SBT), with respect to IMV duration (primary endpoint), extubation failures and reintubations, rate of tracheostomy, intensive care unit (ICU) length of stay and mortality (additional endpoints). All COVID-19 adult patients, intubated for hypoxemic ARF and subsequently extubated, were enrolled. Patients were included in two groups, early extubation followed by immediate NIV application, and conventionally weaning after passing SBT. 121 patients were enrolled and analyzed, 66 early extubated and 55 conventionally weaned after passing an SBT. IMV duration was 9 [6-11] days in early extubated patients versus 11 [6-15] days in standard weaning group (p = 0.034). Extubation failures [12 (18.2%) vs. 25 (45.5%), p = 0.002] and reintubations [12 (18.2%) vs. 22 (40.0%) p = 0.009] were fewer in early extubation compared to the standard weaning groups, respectively. Rate of tracheostomy, ICU mortality, and ICU length of stay were no different between groups. Compared to standard weaning, early extubation followed by immediate NIV shortened IMV duration and reduced the rate of extubation failure and reintubation.

Quantitative Lung Ultrasound: Technical Aspects and Clinical Applications.

Lung ultrasound is increasingly used in emergency departments, medical wards, and critical care units-adult, pediatric, and neonatal. In vitro and in vivo studies show that the number and type of artifacts visualized change with lung density. This has led to the idea of a quantitative lung ultrasound approach, opening up new prospects for use not only as a diagnostic but also as a monitoring tool. Consequently, the multiple scoring systems proposed in the last few years have different technical approaches and specific clinical indications, adaptable for more or less time-dependent patients. However, multiple scoring systems may generate confusion among physicians aiming at introducing lung ultrasound in their clinical practice. This review describes the various lung ultrasound scoring systems and aims to clarify their use in different settings, focusing on technical aspects, validation with reference techniques, and clinical applications.

Diaphragmatic Kinetics Assessment by Tissue Doppler Imaging and Extubation Outcome.

BACKGROUND: The assessment of diaphragmatic kinetics through tissue Doppler imaging (dTDI) was recently proposed as a means to describe diaphragmatic activity in both healthy individuals and intubated patients undergoing weaning from mechanical ventilation. Our primary aim was to investigate whether the diaphragmatic excursion velocity measured with dTDI at the end of a spontaneous breathing trial (SBT) was different in subjects successfully extubated versus those who passed the trial but exhibited extubation failure within 48 h after extubation. METHODS: We enrolled 100 adult subjects, all of whom had successfully passed a 30-min SBT conducted in CPAP of 5 cm H2O. In cases of extubation failure within 48 h after liberation from invasive mechanical ventilation, subjects were re-intubated or supported through noninvasive ventilation. dTDI was performed at the end of the SBT to assess excursion, velocity, and acceleration. RESULTS: Extubation was successful in 79 subjects, whereas it failed in 21 subjects. The median (interquartile range [IQR]) inspiratory peak excursion velocity (3.1 [IQR 2.0-4.3] vs 1.8 [1.3-2.6] cm/s, P < .001), mean velocity (1.6 [IQR 1.2-2.4] vs 1.1 [IQR 0.8-1.4] cm/s, P < .001), and acceleration (8.8 [IQR 5.0-17.8] vs 4.2 [IQR 2.4-8.0] cm/s2, P = .002) were all significantly higher in subjects who failed extubation compared with those who were successfully extubated. Similarly, the median expiratory peak relaxation velocity (2.6 [IQR 1.9-4.5] vs 1.8 [IQR 1.2-2.5] cm/s, P < .001), mean velocity (1.1 [IQR 0.7-1.7] vs 0.9 [IQR 0.6-1.0] cm/s, P = .002), and acceleration (11.2 [IQR 9.1-19.0] vs 7.1 [IQR 4.6-12.0] cm/s2, P = .004) were also higher in the subjects who failed extubation. CONCLUSIONS: In our setting, at the end of SBT, subjects who developed extubation failure within 48 h after extubation experienced a greater diaphragmatic activation compared with subjects who were successfully extubated. (ClinicalTrials.gov registration NCT03962322.).

Outcomes of COVID-19 patients treated with continuous positive airway pressure outside the intensive care unit.

AIM: We aimed to characterise a large population of coronavirus disease 2019 (COVID-19) patients with moderate-to-severe hypoxaemic acute respiratory failure (ARF) receiving continuous positive airway pressure (CPAP) outside the intensive care unit (ICU), and to ascertain whether the duration of CPAP application increased the risk of mortality for patients requiring intubation. METHODS: In this retrospective, multicentre cohort study, we included adult COVID-19 patients, treated with CPAP outside ICU for hypoxaemic ARF from 1 March to 15 April, 2020. We collected demographic and clinical data, including CPAP therapeutic goal, hospital length of stay and 60-day in-hospital mortality. RESULTS: The study included 537 patients with a median (interquartile range (IQR) age of 69 (60-76) years. 391 (73%) were male. According to the pre-defined CPAP therapeutic goal, 397 (74%) patients were included in the full treatment subgroup, and 140 (26%) in the do not intubate (DNI) subgroup. Median (IQR) CPAP duration was 4 (1-8) days, while hospital length of stay was 16 (9-27) days. 60-day in-hospital mortality was 34% (95% CI 0.304-0.384%) overall, and 21% (95% CI 0.169-0.249%) and 73% (95% CI 0.648-0.787%) for full treatment and DNI subgroups, respectively. In the full treatment subgroup, in-hospital mortality was 42% (95% CI 0.345-0.488%) for 180 (45%) CPAP failures requiring intubation, and 2% (95% CI 0.008-0.035%) for the remaining 217 (55%) patients who succeeded. Delaying intubation was associated with increased mortality (hazard ratio 1.093, 95% CI 1.010-1.184). CONCLUSIONS: We described a large population of COVID-19 patients treated with CPAP outside ICU. Intubation delay represents a risk factor for mortality. Further investigation is needed for early identification of CPAP failures.

Neurally adjusted ventilatory assist preserves cerebral blood flow velocity in patients recovering from acute brain injury.

Neurally adjusted ventilatory assist (NAVA) has never been applied in patients recovering from acute brain injury (ABI) because neural respiratory drive could be affected by intracranial disease with detrimental effects on cerebral blood flow (CBF) velocity. Our primary aim was to assess the impact of NAVA and pressure support ventilation (PSV) on CBF velocity. In fifteen adult patients recovering from ABI and undergoing invasive assisted ventilation, PSV and NAVA were applied over 30-min-lasting trials, in the following sequence: PSV1, NAVA, and PSV2. While PSV was set to deliver a tidal volume ranging between 6 and 8 ml kg-1 of predicted body weight, in NAVA the level of assistance was chosen to achieve the same inspiratory peak airway pressure as PSV. At the end of each trial, a sonographic evaluation of CBF mean velocity was bilaterally obtained on the middle cerebral artery and an arterial blood gas sample was taken for analysis. CBF mean velocity was 51.8 [41.9,75.2] cm  s-1 at baseline, 51.9 [43.4,71.0] cm s-1 in PSV1, 53.6 [40.7,67.7] cm s-1 in NAVA, and 49.5 [42.1,70.8] cm s-1 in PSV2 (p = 0.0514) on the left and 50.2 [38.0,77.7] cm s-1 at baseline, 47.8 [41.7,68.2] cm s-1 in PSV1, 53.9 [40.1,78.5] cm s-1 in NAVA, and 55.6 [35.9,74.1] cm s-1 in PSV2 (p = 0.8240) on the right side. No differences were detected for pH (p = 0.0551), arterial carbon dioxide tension (p = 0.8142), and oxygenation (p = 0.0928) over the entire study duration. NAVA and PSV preserved CBF velocity in patients recovering from ABI.Trial registration: The present trial was prospectively registered at www.clinicatrials.gov (NCT03721354) on October 18th, 2018.

Esophageal balloon calibration during Sigh: A physiologic, randomized, cross-over study.

PURPOSE: Optimal esophageal balloon filling volume (Vbest) depends on the intrathoracic pressure. During Sigh breath delivered by the ventilator machine, esophageal balloon is surrounded by elevated intrathoracic pressure that might require higher filling volume for accurate measure of tidal changes in esophageal pressure (Pes). The primary aim of our investigation was to evaluate and compare Vbest during volume controlled and pressure support breaths vs. Sigh breath. MATERIALS AND METHODS: Twenty adult patients requiring invasive volume-controlled ventilation (VCV) for hypoxemic acute respiratory failure were enrolled. After the insertion of a naso-gastric catheter equipped with 10 ml esophageal balloon, each patient underwent three 30-min trials as follows: VCV, pressure support ventilation (PSV), and PSV + Sigh. Sigh was added to PSV as 35 cmH2O pressure-controlled breath over 4 s, once per minute. PSV and PSV + Sigh were randomly applied and, at the end of each step, esophageal balloon calibration was performed. RESULTS: Vbest was higher for Sigh breath (4.5 [3.0-6.8] ml) compared to VCV (1.5 [1.0-2.9] ml, P = 0.0004) and PSV tidal breath (1.0 [0.5-2.4] ml, P < 0.0001). CONCLUSIONS: During Sigh breath, applying a calibrated approach for Pes assessment, a higher Vbest was required compared to VCV and PSV tidal breath.

Critical Care Surge Capacity to Respond to the COVID-19 Pandemic in Italy: A Rapid and Affordable Solution in the Novara Hospital.

The rapid insurgence and spread of coronavirus disease 2019 (COVID-19) exceeded the limit of the intensive care unit (ICU) contingency plan of the Maggiore della Carità University Hospital (Novara, Italy) generating a crisis management condition. This brief report describes how a prompt response to the sudden request of invasive mechanical ventilation (IMV) was provided by addressing the key elements of health care system surge capacity from contingency to crisis. In a short time and at a relatively low cost, a structural modification of a hospital aisle allowed to convert the general ICU into a COVID-19 unit, increasing the number of COVID-19 critical care beds by 107%.

Lung Ultrasound in Patients with Acute Respiratory Failure Reduces Conventional Imaging and Health Care Provider Exposure to COVID-19.

Lung ultrasound gained a leading position in the last year as an imaging technique for the assessment and management of patients with acute respiratory failure. In coronavirus disease 2019 (COVID-19), its role may be of further importance because it is performed bedside and may limit chest X-ray and the need for transport to radiology for computed tomography (CT) scan. Since February 21, we progressively turned into a coronavirus-dedicated intensive care unit and applied an ultrasound-based approach to avoid traditional imaging and limit contamination as much as possible. We performed a complete daily examination with lung ultrasound score computation and systematic search of complications (pneumothorax, ventilator-associated pneumonia); on-duty physicians were free to perform CT or chest X-ray when deemed indicated. We compared conventional imaging exams performed in the first 4 wk of the COVID-19 epidemic with those in the same time frame in 2019: there were 84 patients in 2020 and 112 in 2019; 64 and 22 (76.2% vs. 19.6%, p < 0.001) had acute respiratory failure, respectively, of which 55 (85.9%) were COVID-19 in 2020. When COVID-19 patients in 2020 were compared with acute respiratory failure patients in 2019, the median number of chest X-rays was 1.0 (1.0-2.0) versus 3.0 (1.0-4.0) (p = 0.0098); 2 patients 2 (3.6%) versus 7 patients (31.8%) had undergone at least one thoracic CT scan (p = 0.001). A self-imposed ultrasound-based approach reduces the number of chest X-rays and thoracic CT scans in COVID-19 patients compared with patients with standard acute respiratory failure, thus reducing the number of health care providers exposed to possible contamination and sparing personal protective equipment.

Mechanical Ventilation Guided by Uncalibrated Esophageal Pressure May Be Potentially Harmful.

BACKGROUND: Esophageal balloon calibration was proposed in acute respiratory failure patients to improve esophageal pressure assessment. In a clinical setting characterized by a high variability of abdominal load and intrathoracic pressure (i.e., pelvic robotic surgery), the authors hypothesized that esophageal balloon calibration could improve esophageal pressure measurements. Accordingly, the authors assessed the impact of esophageal balloon calibration compared to conventional uncalibrated approach during pelvic robotic surgery. METHODS: In 30 adult patients, scheduled for elective pelvic robotic surgery, calibrated end-expiratory and end-inspiratory esophageal pressure, and the associated respiratory variations were obtained at baseline, after pneumoperitoneum-Trendelenburg application, and with positive end-expiratory pressure (PEEP) administration and compared to uncalibrated values measured at 4-ml filling volume, as per manufacturer recommendation. Data are expressed as median and [25th, 75th percentile]. RESULTS: Ninety calibrations were successfully performed. Chest wall elastance worsened with pneumoperitoneum-Trendelenburg and PEEP (19.0 [15.5, 24.6] and 16.7 [11.4, 21.7] cm H2O/l) compared to baseline (8.8 [6.3, 9.8] cm H2O/l; P < 0.0001 for both comparisons). End-expiratory and end-inspiratory calibrated esophageal pressure progressively increased from baseline (3.7 [2.2, 6.0] and 7.7 [5.9, 10.2] cm H2O) to pneumoperitoneum-Trendelenburg (6.2 [3.8, 10.2] and 16.1 [13.1, 20.6] cm H2O; P = 0.014 and P < 0.001) and PEEP (8.8 [7.7, 15.6] and 18.9 [16.3, 22.0] cm H2O; P < 0.0001 vs. baseline for both comparison; P < 0.001 and P = 0.002 vs. pneumoperitoneum-Trendelenburg) and, at each study step, they were persistently lower than uncalibrated esophageal pressure (P < 0.0001 for all comparisons). Overall, difference among uncalibrated and calibrated esophageal pressure was 5.1 [3.8, 8.4] cm H2O at end-expiration and 3.8 [3.0, 6.3] cm H2O at end-inspiration. Uncalibrated esophageal pressure swing was always lower than calibrated one (P < 0.0001 for all comparisons) with a difference of -1.0 [-1.8, -0.4] cm H2O. CONCLUSIONS: In a clinical setting with variable chest wall mechanics, uncalibrated measurements substantially overestimated absolute values and underestimated respiratory variations of esophageal pressure. Calibration could substantially improve mechanical ventilation guided by esophageal pressure.

Mechanical ventilation weaning issues can be counted on the fingers of just one hand: part 2.

Assessing heart and diaphragm function constitutes only one of the steps to consider along the weaning path. In this second part of the review, we will deal with the more systematic evaluation of the pulmonary parenchyma-often implicated in the genesis of respiratory failure. We will also consider the other possible causes of weaning failure that lie beyond the cardio-pulmonary-diaphragmatic system. Finally, we will take a moment to consider the remaining unsolved problems arising from mechanical ventilation and describe the so-called protective approach to parenchyma and diaphragm ventilation.

Oesophageal balloon calibration during pressure support ventilation: a proof of concept study.

Oesophageal balloon calibration improves the oesophageal pressure (Pes) assessment during invasive controlled mechanical ventilation. The primary aim of the present investigation was to ascertain the feasibility of oesophageal balloon calibration during pressure support ventilation (PSV). Secondarily, the calibrated Pes (Pescal) was compared to uncalibrated one acquired at 4 ml-filling volume (PesV4), as per manufacturer recommendation. After a naso-gastric tube equipped with oesophageal balloon was correctly positioned in 21 adult patients undergoing invasive volume-controlled ventilation (VCV) for acute hypoxemic respiratory failure, the balloon was progressively inflated, applying a series of end-inspiratory and end-expiratory holds at each filling volume during VCV and PSV. Upon optimal balloon filling volume (Vbest) was identified, Pescal was computed by correcting the Pes measured at Vbest for the oesophageal wall pressure elicited at same filling volume. Finally, end-expiratory and end-inspiratory PesV4 were recorded too. A total of 42 calibrations, 21 per ventilatory mode, were performed. Vbest was 1.9 ± 1.6 ml in VCV and 1.7 ± 1.6 ml in PSV (p = 0.5217). PesV4 was overestimated compared to Pescal at end-expiration and end-inspiration (p <0.0001 for all comparisons) in both VCV (13.4 ± 3.4 cmH2O and 15.4 ± 3 cmH2O vs. 8.5 ± 2.9 cmH2O and 11.4 ± 3 cmH2O) and PSV (14.7 ± 4.2 cmH2O and 17 ± 3.9 cmH2O vs. 8.9 ± 3.4 cmH2O and 12.4 ± 3.9 cmH2O). In PSV, oesophageal balloon calibration is feasible and allows to obtain a reliable Pes assessment compared to uncalibrated approach.

Perilipin 2 levels are increased in patients with in-stent neoatherosclerosis: A clue to mechanisms of accelerated plaque formation after drug-eluting stent implantation.

BACKGROUND: Perilipin 2 (PLIN2) is a protein that potentially facilitates atherogenesis in native coronary arteries or arteries with an implanted drug-eluting stent (DES). The aim of the study was to determine PLIN2 protein levels in peripheral monocytes of enrolled subjects and compare them between patients with native coronary artery disease (CAD) and those with an in-stent restenosis (ISR) due to neoatherosclerosis occurring >1 year after DES implantation. METHODS: Forty-two patients were prospectively enrolled in the study in 3:1 fashion and underwent coronary catheterization. Both groups were angiographically matched for CAD burden with respect to the number of diseased vessels. Neoatherosclerosis was determined by intracoronary optical coherence tomography (OCT) among patients with ISR. RESULTS: Patients with ISR due to neoatherosclerosis had significantly higher PLIN2 protein levels in peripheral blood monocytes compared to patients with native CAD (342.47 ±â€¯75.63[SE] versus 119.51 ±â€¯20.95, p < 0.001). PLIN2 protein levels did not significantly differ between unstable and stable disease phenotype (125.59 ±â€¯131.02 vs. 146.14 ±â€¯111.87, p = 0.109). CONCLUSIONS: In this explorative study, PLIN2 protein levels are significantly increased in patients with neoatherosclerosis, irrespective of clinical presentation, implicating that it might play a pathogenetic role in accelerated atherosclerosis after DES implantation. Further larger clinical studies are warranted to confirm these initial findings.