A pragmatic, open-label, multi-center, randomized controlled clinical trial on the rotational use of interfaces vs standard of care in patients treated with noninvasive positive pressure ventilation for acute hypercapnic respiratory failure: the ROTAtional-USE of interface STUDY (ROTA-USE STUDY).

BACKGROUND: In the last decades, noninvasive ventilation (NIV) has been increasingly used to support patients with hypercapnic and hypoxemic acute respiratory failure. Pressure ulcers are a frequently observed NIV-related adverse effect, directly related to interface type and exposure time. Switching to a different interface has been proposed as a solution to improve patient comfort. However, large studies investigating the benefit of this strategy are not available. Thus, the aim of the ROTAtional-USE of interface STUDY (ROTA-USE STUDY) is to investigate whether a protocolized rotational use of interfaces during NIV is effective in reducing the incidence of pressure ulcers. METHODS: The ROTA-USE STUDY is a pragmatic, parallel arm, open-label, multicenter, spontaneous, non-profit, randomized controlled trial requiring non-significant risk medical devices, with the aim to determine whether a rotational strategy of NIV interfaces is associated with a lower incidence of pressure ulcers compared to the standard of care. In the intervention group, NIV mask will be randomly chosen and rotated every 6 h. In the control group, mask will be chosen according to the standard of care of the participating centers and changed in case of discomfort or in the presence of new pressure sores. In both groups, the skin underneath the mask will be inspected every 12 h for any possible damage by blinded assessors. The primary outcome is the proportion of patients developing new pressure sores at 36 h from randomization. The secondary outcomes are (i) onset of pressure sores measured at different time points, i.e., 12, 24, 36, 48, 60, 72, 84, and 96 h; (ii) number and stage of pressure sores and comfort measured at 12, 24, 36, 48, 60, 72, 84, and 96 h; and (iii) the economic impact of the protocolized rotational use of interfaces. A sample size of 239 subjects per group (intervention and control) is estimated to detect a 10% absolute difference in the proportion of patients developing pressure sores at 36 h. DISCUSSION: The development of pressure ulcers is a common side effect of NIV that negatively affects the patients' comfort and tolerance, often leading to NIV failure and adverse outcomes. The ROTA-USE STUDY will determine whether a protocolized rotational approach can reduce the incidence, number, and severity of pressure ulcers in NIV-treated patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT05513508. Registered on August 24, 2022.

Tidal volume challenge to predict preload responsiveness in patients with acute respiratory distress syndrome under prone position.

BACKGROUND: Prone position is frequently used in patients with acute respiratory distress syndrome (ARDS), especially during the Coronavirus disease 2019 pandemic. Our study investigated the ability of pulse pressure variation (PPV) and its changes during a tidal volume challenge (TVC) to assess preload responsiveness in ARDS patients under prone position. METHODS: This was a prospective study conducted in a 25-bed intensive care unit at a university hospital. We included patients with ARDS under prone position, ventilated with 6 mL/kg tidal volume and monitored by a transpulmonary thermodilution device. We measured PPV and its changes during a TVC (ΔPPV TVC6-8) after increasing the tidal volume from 6 to 8 mL/kg for one minute. Changes in cardiac index (CI) during a Trendelenburg maneuver (ΔCITREND) and during end-expiratory occlusion (EEO) at 8 mL/kg tidal volume (ΔCI EEO8) were recorded. Preload responsiveness was defined by both ΔCITREND ≥ 8% and ΔCI EEO8 ≥ 5%. Preload unresponsiveness was defined by both ΔCITREND < 8% and ΔCI EEO8 < 5%. RESULTS: Eighty-four sets of measurements were analyzed in 58 patients. Before prone positioning, the ratio of partial pressure of arterial oxygen to fraction of inspired oxygen was 104 ± 27 mmHg. At the inclusion time, patients were under prone position for 11 (2-14) hours. Norepinephrine was administered in 83% of cases with a dose of 0.25 (0.15-0.42) µg/kg/min. The positive end-expiratory pressure was 14 (11-16) cmH2O. The driving pressure was 12 (10-17) cmH2O, and the respiratory system compliance was 32 (22-40) mL/cmH2O. Preload responsiveness was detected in 42 cases. An absolute change in PPV ≥ 3.5% during a TVC assessed preload responsiveness with an area under the receiver operating characteristics (AUROC) curve of 0.94 ± 0.03 (sensitivity: 98%, specificity: 86%) better than that of baseline PPV (0.85 ± 0.05; p = 0.047). In the 56 cases where baseline PPV was inconclusive (≥ 4% and < 11%), ΔPPV TVC6-8 ≥ 3.5% still enabled to reliably assess preload responsiveness (AUROC: 0.91 ± 0.05, sensitivity: 97%, specificity: 81%; p < 0.01 vs. baseline PPV). CONCLUSION: In patients with ARDS under low tidal volume ventilation during prone position, the changes in PPV during a TVC can reliably assess preload responsiveness without the need for cardiac output measurements. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04457739). Registered 30 June 2020 -Retrospectively registered, https://clinicaltrials.gov/ct2/show/record/NCT04457739.

The Role of Lung Ultrasound Monitoring in Early Detection of Ventilator-Associated Pneumonia in COVID-19 Patients: A Retrospective Observational Study.

Specific lung ultrasound signs combined with clinical parameters allow for early diagnosis of ventilator-associated pneumonia in the general ICU population. This retrospective cohort study aimed to determine the accuracy of lung ultrasound monitoring for ventilator-associated pneumonia diagnosis in COVID-19 patients. Clinical (i.e., clinical pulmonary infection score) and ultrasound (i.e., presence of consolidation and a dynamic linear−arborescent air bronchogram, lung ultrasound score, ventilator-associated lung ultrasound score) data were collected on the day of the microbiological sample (pneumonia-day) and 48 h before (baseline) on 55 bronchoalveolar lavages of 33 mechanically-ventilated COVID-19 patients who were monitored daily with lung ultrasounds. A total of 26 samples in 23 patients were positive for ventilator-associated pneumonia (pneumonia cases). The onset of a dynamic linear−arborescent air bronchogram was 100% specific for ventilator-associated pneumonia. The ventilator-associated lung ultrasound score was higher in pneumonia-cases (2.5 (IQR 1.0 to 4.0) vs. 1.0 (IQR 1.0 to 1.0); p < 0.001); the lung ultrasound score increased from baseline in pneumonia-cases only (3.5 (IQR 2.0 to 6.0) vs. −1.0 (IQR −2.0 to 1.0); p = 0.0001). The area under the curve for clinical parameters, ventilator-associated pneumonia lung ultrasound score, and lung ultrasound score variations were 0.472, 0.716, and 0.800, respectively. A newly appeared dynamic linear−arborescent air bronchogram is highly specific for ventilator-associated pneumonia in COVID-19 patients. A high ventilator-associated pneumonia lung ultrasound score (or an increase in the lung ultrasound score) orients to ventilator-associated pneumonia.

Clinical Outcomes in Patients Aged 80 Years or Older Receiving Non-Invasive Respiratory Support for Hypoxemic Acute Respiratory Failure Consequent to COVID-19.

As the clinical outcome of octogenarian patients hospitalised for COVID-19 is very poor, here we assessed the clinical characteristics and outcomes of patients aged 80 year or older hospitalised for COVID-19 receiving non-invasive respiratory support (NIRS). A multicentre, retrospective, observational study was conducted in seven hospitals in Northern Italy. All patients aged ≥80 years with COVID-19 associated hypoxemic acute respiratory failure (hARF) undergoing NIRS between 24 February 2020, and 31 March 2021, were included. Out of 252 study participants, 156 (61.9%) and 163 (64.6%) died during hospital stay and within 90 days from hospital admission, respectively. In this case, 228 (90.5%) patients only received NIRS (NIRS group), while 24 (9.5%) were treated with invasive mechanical ventilation (IMV) after NIRS failure (NIRS+IMV group). In-hospital mortality did not significantly differ between NIRS and NIRS+IMV group (61.0% vs. 70.8%, respectively; p = 0.507), while survival probability at 90 days was significantly higher for NIRS compared to NIRS+IMV patients (0.379 vs. 0.147; p = 0.0025). The outcome of octogenarian patients with COVID-19 receiving NIRS is quite poor. Caution should be used when considering transition from NIRS to IMV after NIRS 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.

Bioreactance reliably detects preload responsiveness by the end-expiratory occlusion test when averaging and refresh times are shortened.

BACKGROUND: The end-expiratory occlusion (EEXPO) test detects preload responsiveness, but it is 15 s long and induces small changes in cardiac index (CI). It is doubtful whether the Starling bioreactance device, which averages CI over 24 s and refreshes the displayed value every 4 s (Starling-24.4), can detect the EEXPO-induced changes in CI (ΔCI). Our primary goal was to test whether this Starling device version detects preload responsiveness through EEXPO. We also tested whether shortening the averaging and refresh times to 8 s and one second, respectively, (Starling-8.1) improves the accuracy of the device in detecting preload responsiveness using EEXPO. METHODS: In 42 mechanically ventilated patients, during a 15-s EEXPO, we measured ∆CI through calibrated pulse contour analysis (CIpulse, PiCCO2 device) and using the Starling device. For the latter, we considered both CIStarling-24.4 from the commercial version and CIStarling-8.1 derived from the raw data. For relative ∆CIStarling-24.4 and ∆CIStarling-8.1 during EEXPO, we calculated the area under the receiver operating characteristic curve (AUROC) to detect preload responsiveness, defined as an increase in CIpulse ≥ 10% during passive leg raising (PLR). For both methods, the correlation coefficient vs. ∆CIpulse was calculated. RESULTS: Twenty-six patients were preload responders and sixteen non preload-responders. The AUROC for ∆CIStarling-24.4 was significantly lower compared to ∆CIStarling-8.1 (0.680 ± 0.086 vs. 0.899 ± 0.049, respectively; p = 0.027). A significant correlation was observed between ∆CIStarling-8.1 and ∆CIpulse (r = 0.42; p = 0.009), but not between ∆CIStarling-24.4 and ∆CIpulse. During PLR, both ∆CIStarling-24.4 and ∆CIStarling-8.1 reliably detected preload responsiveness. CONCLUSIONS: Shortening the averaging and refresh times of the bioreactance signal to 8 s and one second, respectively, increases the reliability of the Starling device in detection of EEXPO-induced ∆CI. TRIAL REGISTRATION: No. IDRCB: 2018-A02825-50. Registered 13 December 2018.

COVID-19 ARDS is characterized by higher extravascular lung water than non-COVID-19 ARDS: the PiCCOVID study.

BACKGROUND: In acute respiratory distress syndrome (ARDS), extravascular lung water index (EVLWi) and pulmonary vascular permeability index (PVPI) measured by transpulmonary thermodilution reflect the degree of lung injury. Whether EVLWi and PVPI are different between non-COVID-19 ARDS and the ARDS due to COVID-19 has never been reported. We aimed at comparing EVLWi, PVPI, respiratory mechanics and hemodynamics in patients with COVID-19 ARDS vs. ARDS of other origin. METHODS: Between March and October 2020, in an observational study conducted in intensive care units from three university hospitals, 60 patients with COVID-19-related ARDS monitored by transpulmonary thermodilution were compared to the 60 consecutive non-COVID-19 ARDS admitted immediately before the COVID-19 outbreak between December 2018 and February 2020. RESULTS: Driving pressure was similar between patients with COVID-19 and non-COVID-19 ARDS, at baseline as well as during the study period. Compared to patients without COVID-19, those with COVID-19 exhibited higher EVLWi, both at the baseline (17 (14-21) vs. 15 (11-19) mL/kg, respectively, p = 0.03) and at the time of its maximal value (24 (18-27) vs. 21 (15-24) mL/kg, respectively, p = 0.01). Similar results were observed for PVPI. In COVID-19 patients, the worst ratio between arterial oxygen partial pressure over oxygen inspired fraction was lower (81 (70-109) vs. 100 (80-124) mmHg, respectively, p = 0.02) and prone positioning and extracorporeal membrane oxygenation (ECMO) were more frequently used than in patients without COVID-19. COVID-19 patients had lower maximal lactate level and maximal norepinephrine dose than patients without COVID-19. Day-60 mortality was similar between groups (57% vs. 65%, respectively, p = 0.45). The maximal value of EVLWi and PVPI remained independently associated with outcome in the whole cohort. CONCLUSION: Compared to ARDS patients without COVID-19, patients with COVID-19 had similar lung mechanics, but higher EVLWi and PVPI values from the beginning of the disease. This was associated with worse oxygenation and with more requirement of prone positioning and ECMO. This is compatible with the specific lung inflammation and severe diffuse alveolar damage related to COVID-19. By contrast, patients with COVID-19 had fewer hemodynamic derangement. Eventually, mortality was similar between groups. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION: ClinicalTrials.gov (NCT04337983). Registered 30 March 2020-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04337983 .

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.

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.

Circulating Platelet-Derived Extracellular Vesicles Are a Hallmark of Sars-Cov-2 Infection.

Sars-Cov-2 infection causes fever and cough that may rapidly lead to acute respiratory distress syndrome (ARDS). Few biomarkers have been identified but, unfortunately, these are individually poorly specific, and novel biomarkers are needed to better predict patient outcome. The aim of this study was to evaluate the diagnostic performance of circulating platelets (PLT)-derived extracellular vesicles (EVs) as biomarkers for Sars-Cov-2 infection, by setting a rapid and reliable test on unmanipulated blood samples. PLT-EVs were quantified by flow cytometry on two independent cohorts of Sars-CoV-2+ (n = 69), Sars-Cov-2- (n = 62) hospitalized patients, and healthy controls. Diagnostic performance of PLT-EVs was evaluated by receiver operating characteristic (ROC) curve. PLT-EVs count were higher in Sars-Cov-2+ compared to Sars-Cov-2- patients or HC. ROC analysis of the combined cohorts showed an AUC = 0.79 and an optimal cut-off value of 1472 EVs/µL, with 75% sensitivity and 74% specificity. These data suggest that PLT-EVs might be an interesting biomarker deserving further investigations to test their predictive power.

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.

Changes in the Plethysmographic Perfusion Index During an End-Expiratory Occlusion Detect a Positive Passive Leg Raising Test.

OBJECTIVES: The end-expiratory occlusion test for assessing preload responsiveness consists in interrupting mechanical ventilation for 15 seconds at end-expiration and measuring the cardiac index changes. The perfusion index is the ratio between the pulsatile and the nonpulsatile portions of the plethysmography signal and is, in part, determined by stroke volume. We tested whether the end-expiratory occlusion-induced changes in perfusion index could detect a positive passive leg raising test, suggesting preload responsiveness. DESIGN: Observational study. SETTING: Medical ICU. PATIENTS: Thirty-one ventilated patients without atrial fibrillation. INTERVENTIONS: We measured perfusion index (Radical-7 device; Masimo Corp., Irvine, CA) and cardiac index (PiCCO2; Pulsion Medical Systems, Feldkirchen, Germany) before and during a passive leg raising test and a 15-second end-expiratory occlusion. MEASUREMENTS AND MAIN RESULTS: In 19 patients with a positive passive leg raising test (increase in cardiac index ≥ 10%), compared to the baseline value and expressed as a relative change, passive leg raising increased cardiac index and perfusion index by 17% ± 7% and 49% ± 23%, respectively, In these patients, end-expiratory occlusion increased cardiac index and perfusion index by 6% ± 2% and 11% ± 8%, respectively. In the 12 patients with a negative passive leg raising test, perfusion index did not significantly change during passive leg raising and end-expiratory occlusion. Relative changes in perfusion index and cardiac index observed during all interventions were significantly correlated (r = 0.83). An end-expiratory occlusion-induced relative increase in perfusion index greater than or equal to 2.5% ([perfusion index during end-expiratory occlusion-perfusion index at baseline]/perfusion index at baseline × 100) detected a positive passive leg raising test with an area under the receiver operating characteristic curve of 0.95 ± 0.03. This threshold is larger than the least significant change observed for perfusion index (1.62% ± 0.80%). CONCLUSIONS: Perfusion index could be used as a reliable surrogate of cardiac index for performing the end-expiratory occlusion test. Confirming previous results, the relative changes in perfusion index also reliably detected a positive passive leg raising test.

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.

Vasopressors in septic shock: which, when, and how much?

In addition to fluid resuscitation, the vasopressor therapy is a fundamental treatment of septic shock-induced hypotension as it aims at correcting the vascular tone depression and then at improving organ perfusion pressure. Experts' recommendations currently position norepinephrine (NE) as the first-line vasopressor in septic shock. Vasopressin and its analogues are only second-line vasopressors as strong recent evidence suggests no benefit of their early administration in spite of promising preliminary data. Early administration of NE may allow achieving the initial mean arterial pressure (MAP) target faster and reducing the risk of fluid overload. The diastolic arterial pressure (DAP) as a marker of vascular tone, helps identifying the patients who need NE urgently. Available data suggest a MAP of 65 mmHg as the initial target but a more individualized approach is often required depending on several factors such as history of chronic hypertension or value of central venous pressure (CVP). In cases of refractory hypotension, increasing NE up to doses ≥1 µg/kg/min could be an option. However, current experts' guidelines suggest to combine NE with other vasopressors such as vasopressin, with the intent to rising the MAP to target or to decrease the NE dosage.

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%.

Predicted Effects of Stopping COVID-19 Lockdown on Italian Hospital Demand.

OBJECTIVES: Italy has been one of the first countries to implement mitigation measures to curb the coronavirus disease 2019 (COVID-19) pandemic. There is currently a debate on when and how such measures should be loosened. To forecast the demand for hospital intensive care unit (ICU) and non-ICU beds for COVID-19 patients from May to September, we developed 2 models, assuming a gradual easing of restrictions or an intermittent lockdown. METHODS: We used a compartmental model to evaluate 2 scenarios: (A) an intermittent lockdown; (B) a gradual relaxation of the lockdown. Predicted ICU and non-ICU demand was compared with the peak in hospital bed use observed in April 2020. RESULTS: Under scenario A, while ICU demand will remain below the peak, the number of non-ICU will substantially rise and will exceed it (133%; 95% confidence interval [CI]: 94-171). Under scenario B, a rise in ICU and non-ICU demand will start in July and will progressively increase over the summer 2020, reaching 95% (95% CI: 71-121) and 237% (95% CI: 191-282) of the April peak. CONCLUSIONS: Italian hospital demand is likely to remain high in the next months. If restrictions are reduced, planning for the next several months should consider an increase in health-care resources to maintain surge capacity across the country.