Thoracic UltrasONOgraphy Reporting: The TUONO Consensus.

The widespread use of the lung ultrasound (LUS) has not been followed by the development of a comprehensive standardized tool for its reporting in the intensive care unit (ICU) which could be useful to promote consistency and reproducibility during clinical examination. This work aims to define the essential features to be included in a standardized reporting tool and provides a structured model form to fully express the diagnostic potential of LUS and facilitate intensivists in the use of a LUS in everyday clinical ICU examination. We conducted a modified Delphi process to build consensus on the items to be integrated in a standardized report form and on its structure. A committee of 19 critical care physicians from 19 participating ICUs in Italy was formed, including intensivists experienced in ultrasound from both teaching hospitals and referral hospitals, and internationally renowned experts on the LUS. The consensus for 31 statements out of 33 was reached at the third Delphi round. A structured model form was developed based on the approved statements. The development of a standardized model as a backbone to report a LUS may facilitate the guidelines' application in clinical practice and increase inter-operator agreement. Further studies are needed to evaluate the effects of standardized reports in critically ill patients.

COVID-19 Detection Using Photoplethysmography and Neural Networks.

The early identification of microvascular changes in patients with Coronavirus Disease 2019 (COVID-19) may offer an important clinical opportunity. This study aimed to define a method, based on deep learning approaches, for the identification of COVID-19 patients from the analysis of the raw PPG signal, acquired with a pulse oximeter. To develop the method, we acquired the PPG signal of 93 COVID-19 patients and 90 healthy control subjects using a finger pulse oximeter. To select the good quality portions of the signal, we developed a template-matching method that excludes samples corrupted by noise or motion artefacts. These samples were subsequently used to develop a custom convolutional neural network model. The model accepts PPG signal segments as input and performs a binary classification between COVID-19 and control samples. The proposed model showed good performance in identifying COVID-19 patients, achieving 83.86% accuracy and 84.30% sensitivity (hold-out validation) on test data. The obtained results indicate that photoplethysmography may be a useful tool for microcirculation assessment and early recognition of SARS-CoV-2-induced microvascular changes. In addition, such a noninvasive and low-cost method is well suited for the development of a user-friendly system, potentially applicable even in resource-limited healthcare settings.

Automatic COVID-19 severity assessment from HRV.

COVID-19 is known to be a cause of microvascular disease imputable to, for instance, the cytokine storm inflammatory response and the consequent blood coagulation. In this study, we propose a methodological approach for assessing the COVID-19 presence and severity based on Random Forest (RF) and Support Vector Machine (SVM) classifiers. Classifiers were applied to Heart Rate Variability (HRV) parameters extracted from photoplethysmographic (PPG) signals collected from healthy and COVID-19 affected subjects. The supervised classifiers were trained and tested on HRV parameters obtained from the PPG signals in a cohort of 50 healthy subjects and 93 COVID-19 affected subjects, divided into two groups, mild and moderate, based on the support of oxygen therapy and/or ventilation. The most informative feature set for every group's comparison was determined with the Least Absolute Shrinkage and Selection Operator (LASSO) technique. Both RF and SVM classifiers showed a high accuracy percentage during groups' comparisons. In particular, the RF classifier reached 94% of accuracy during the comparison between the healthy and minor severity COVID-19 group. Obtained results showed a strong capability of RF and SVM to discriminate between healthy subjects and COVID-19 patients and to differentiate the two different COVID-19 severity. The proposed method might be helpful for detecting, in a low-cost and fast fashion, the presence and severity of COVID-19 disease; moreover, these reasons make this method interesting as a starting point for future studies that aim to investigate its effectiveness as a possible screening method.

Thoracic UltrasONOgraphy Reporting: The TUONO Study.

Lung ultrasound (LUS) is a validated technique for the prompt diagnosis and bedside monitoring of critically ill patients due to its availability, safety profile, and cost-effectiveness. The aim of this work is to detect similarities and differences among LUS reports performed in ICUs and to provide a common ground for an integrated report form. We collected all LUS reports during an index week in 21 ICUs from the GiViTI network. First, we considered signs, chest areas, and terminology reported. Then, we compared different report structures and categorized them as structured reports (SRs), provided with a predefined model form, and free unstructured text reports (FTRs) that had no predetermined structure. We analyzed 171 reports from 21 ICUs, and 59 reports from 5 ICUs were structured. All the reports presented a qualitative description that mainly focused on the presence of B-lines, consolidations, and pleural effusion. Zones were defined in 66 reports (39%). In SRs, a complete examination of all the regions was more frequently achieved (96% vs. 74%), and a higher impact on therapeutic strategies was observed (17% vs. 6%). LUS reports vary significantly among different centers. Adopting an integrated SR seems to promote a systematic approach in scanning and reporting, with a potential impact on LUS clinical applications.

Classifying sepsis from photoplethysmography.

Sepsis is a life-threatening organ dysfunction. It is caused by a dysregulated immune response to an infection and is one of the leading causes of death in the intensive care unit (ICU). Early detection and treatment of sepsis can increase the survival rate of patients. The use of devices such as the photoplethysmograph could allow the early evaluation in addition to continuous monitoring of septic patients. The aim of this study was to verify the possibility of detecting sepsis in patients from whom the photoplethysmographic signal was acquired via a pulse oximeter. In this work, we developed a deep learning-based model for sepsis identification. The model takes a single input, the photoplethysmographic signal acquired by pulse oximeter, and performs a binary classification between septic and nonseptic samples. To develop the method, we used MIMIC-III database, which contains data from ICU patients. Specifically, the selected dataset includes 85 septic subjects and 101 control subjects. The PPG signals acquired from these patients were segmented, processed and used as input for the developed model with the aim of identifying sepsis. The proposed method achieved an accuracy of 76.37% with a sensitivity of 70.95% and a specificity of 81.04% on the test set. As regards the ROC curve, the Area Under Curve reached a value of 0.842. The results of this study indicate how the plethysmographic signal can be used as a warning sign for the early detection of sepsis with the aim of reducing the time for diagnosis and therapeutic intervention. Furthermore, the proposed method is suitable for integration in continuous patient monitoring.

COVID-19 detection using a model of photoplethysmography (PPG) signals.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) targets several tissues of the human body; among these, a serious impact has been observed in the microvascular system. The aim of this study was to verify the presence of photoplethysmographic (PPG) signal modifications in patients affected by COVID-19 at different levels of severity. APPROACH: The photoplethysmographic signal was evaluated in 93 patients with COVID-19 of different severity (46: grade 1; 47: grade 2) and in 50 healthy control subjects. A pre-processing step removes the long-term trend and segments of each pulsation in the input signal. Each pulse is approximated with a model generated from a multi-exponential curve, and a Least Squares fitting algorithm determines the optimal model parameters. Using the parameters of the mathematical model, three different classifiers (Bayesian, SVM and KNN) were trained and tested to discriminate among healthy controls and patients with COVID, stratified according to the severity of the disease. Results are validated with the leave-one-subject-out validation method. MAIN RESULTS: Results indicate that the fitting procedure obtains a very high determination coefficient (above 99% in both controls and pathological subjects). The proposed Bayesian classifier obtains promising results, given the size of the dataset, and variable depending on the classification strategy. The optimal classification strategy corresponds to 79% of accuracy, with 90% of specificity and 67% of sensibility. SIGNIFICANCE: The proposed approach opens the possibility of introducing a low cost and non-invasive screening procedure for the fast detection of COVID-19 disease, as well as a promising monitoring tool for hospitalized patients, with the purpose of stratifying the severity of the disease.

Cardiovascular Dynamics in COVID-19: A Heart Rate Variability Investigation.

COVID-19 is known to be a cause of microvascular disease due, for example, to the cytokine storm inflammatory response and the result of blood coagulation. This study reports an investigation on Heart Rate Variability (HRV) extracted from photoplethysmography (PPG) signals measured from healthy subjects and COVID-19 affected patients. We aimed to determine a statistical difference between HRV parameters among subjects' groups. Specifically, statistical analysis through Mann-Whitney U Test (MWUT) was applied to compare 42 dif-ferent parameters extracted from PPG signals of 143 subjects: 50 healthy subjects (i.e. group 0) and 93 affected from COVID-19 patients stratified through increasing COVID severity index (i.e. groups 1 and 2). Results showed significant statistical differences between groups in several HRV parameters. In particular, Multiscale Entropy (MSE) analysis provided the master key in patient stratification assessment. In fact, MSE11, MSE12, MSE15, MSE16, MSE17, MSE18, MSE19 and MSE20 keep statistical significant difference during all the comparisons between healthy subjects and patients from all the pathological groups. Our preliminary results suggest that it could be possible to distinguish between healthy and COVID-19 affected subjects based on cardiovascular dynamics. This study opens to future evaluations in using machine learning models for automatic decision-makers to distinguish between healthy and COVID-19 subjects, as well as within COVID-19 severity levels. Clinical Relevance - This establishes the possibility to distin-guish healthy subjects from COVID-19 affected patients basing on HRV parameters monitored non invasively by PPG.

Hospitals with and without neurosurgery: a comparative study evaluating the outcome of patients with traumatic brain injury.

BACKGROUND: We leveraged the data of the international CREACTIVE consortium to investigate whether the outcome of traumatic brain injury (TBI) patients admitted to intensive care units (ICU) in hospitals without on-site neurosurgical capabilities (no-NSH) would differ had the same patients been admitted to ICUs in hospitals with neurosurgical capabilities (NSH). METHODS: The CREACTIVE observational study enrolled more than 8000 patients from 83 ICUs. Adult TBI patients admitted to no-NSH ICUs within 48 h of trauma were propensity-score matched 1:3 with patients admitted to NSH ICUs. The primary outcome was the 6-month extended Glasgow Outcome Scale (GOS-E), while secondary outcomes were ICU and hospital mortality. RESULTS: A total of 232 patients, less than 5% of the eligible cohort, were admitted to no-NSH ICUs. Each of them was matched to 3 NSH patients, leading to a study sample of 928 TBI patients where the no-NSH and NSH groups were well-balanced with respect to all of the variables included into the propensity score. Patients admitted to no-NSH ICUs experienced significantly higher ICU and in-hospital mortality. Compared to the matched NSH ICU admissions, their 6-month GOS-E scores showed a significantly higher prevalence of upper good recovery for cases with mild TBI and low expected mortality risk at admission, along with a progressively higher incidence of poor outcomes with increased TBI severity and mortality risk. CONCLUSIONS: In our study, centralization of TBI patients significantly impacted short- and long-term outcomes. For TBI patients admitted to no-NSH centers, our results suggest that the least critically ill can effectively be managed in centers without neurosurgical capabilities. Conversely, the most complex patients would benefit from being treated in high-volume, neuro-oriented ICUs.

Prognostic determinants in patients with non traumatic intracerebral hemorrhage: a real life report.

Background and aim: Nontraumatic intracerebral hemorrhage (ICH) remains a devastating disease for high in-hospital and long-term mortality and residual neurological disability. The aim of our study was to analyze the prognostic factors in patients managed for ICH in the real-life clinical practice.Materials and Methods: We retrospectively analyzed clinical and neuro-radiological data of consecutive patients admitted to our Hospital for ICH along 1 year. In-hospital mortality and 90-day modified Rankin scale (mRS) ≥4 were the study outcomes. Moreover, we compared patients admitted in Intensive Care Unit (ICU) with patients admitted in Stroke Unit (SU).Results: Ninety-eight patients with mean age ± SD 78 ± 12 years were enrolled. In-hospital and 90-day mortality were 36.7% and 41.8%, respectively. Patients who died had a significantly higher percentage of ICH volume >30 mL, irregular shape, lobar location, intraventricular hemorrhage (IVH), midline shift, hydrocephalus, hematoma enlargement, Glasgow Coma Scale (GCS) ≤9 at hospital admission, early neurological worsening (ENW), higher Hemphill ICH score, and underwent oro-tracheal intubation more frequently compared with patients who survived. Patients admitted to ICU were younger and significantly more critical compared with those who were admitted to SU. In-hospital mortality in patients admitted to ICU was 52.6% compared with 25% in patients admitted to SU (p < 0.01). Median mRS score at hospital discharge was 4 (IQR 3-5) and at 90 days was 4 (IQR 3-4). ENW, hematoma enlargement, Hemphill ICH score ≥3 and midline shift >10 mm were found independent risk factors for in-hospital mortality, while age was found as independent risk factor for 90-day mRS ≥4).Conclusion: In real life, prognosis of ICH is associated with clinical and radiological determinants. In our study ENW, hematoma enlargement, Hemphill ICH score ≥3 and midline shift >10 mm were associated with short-term mortality risk, while age with 90-day mRS ≥4.

Sigh in Patients With Acute Hypoxemic Respiratory Failure and ARDS: The PROTECTION Pilot Randomized Clinical Trial.

BACKGROUND: Sigh is a cyclic brief recruitment maneuver: previous physiologic studies showed that its use could be an interesting addition to pressure support ventilation to improve lung elastance, decrease regional heterogeneity, and increase release of surfactant. RESEARCH QUESTION: Is the clinical application of sigh during pressure support ventilation (PSV) feasible? STUDY DESIGN AND METHODS: We conducted a multicenter noninferiority randomized clinical trial on adult intubated patients with acute hypoxemic respiratory failure or ARDS undergoing PSV. Patients were randomized to the no-sigh group and treated by PSV alone, or to the sigh group, treated by PSV plus sigh (increase in airway pressure to 30 cm H2O for 3 s once per minute) until day 28 or death or successful spontaneous breathing trial. The primary end point of the study was feasibility, assessed as noninferiority (5% tolerance) in the proportion of patients failing assisted ventilation. Secondary outcomes included safety, physiologic parameters in the first week from randomization, 28-day mortality, and ventilator-free days. RESULTS: Two-hundred and fifty-eight patients (31% women; median age, 65 [54-75] years) were enrolled. In the sigh group, 23% of patients failed to remain on assisted ventilation vs 30% in the no-sigh group (absolute difference, -7%; 95% CI, -18% to 4%; P = .015 for noninferiority). Adverse events occurred in 12% vs 13% in the sigh vs no-sigh group (P = .852). Oxygenation was improved whereas tidal volume, respiratory rate, and corrected minute ventilation were lower over the first 7 days from randomization in the sigh vs no-sigh group. There was no significant difference in terms of mortality (16% vs 21%; P = .337) and ventilator-free days (22 [7-26] vs 22 [3-25] days; P = .300) for the sigh vs no-sigh group. INTERPRETATION: Among hypoxemic intubated ICU patients, application of sigh was feasible and without increased risk. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT03201263; URL: www.clinicaltrials.gov.

Pressure support ventilation + sigh in acute hypoxemic respiratory failure patients: study protocol for a pilot randomized controlled trial, the PROTECTION trial.

BACKGROUND: Adding cyclic short sustained inflations (sigh) to assisted ventilation yields optimizes lung recruitment, decreases heterogeneity and reduces inspiratory effort in patients with acute hypoxemic respiratory failure (AHRF). These findings suggest that adding sigh to pressure support ventilation (PSV) might decrease the risk of lung injury, shorten weaning and improve clinical outcomes. Thus, we conceived a pilot trial to test the feasibility of adding sigh to PSV (the PROTECTION study). METHODS: PROTECTION is an international randomized controlled trial that will be conducted in 23 intensive care units (ICUs). Patients with AHRF who have been intubated from 24 h to 7 days and undergoing PSV from 4 to 24 h will be enrolled. All patients will first undergo a 30-min sigh test by adding sigh to clinical PSV for 30 min to identify early oxygenation responders. Then, patients will be randomized to PSV or PSV + sigh until extubation, ICU discharge, death or day 28. Sigh will be delivered as a 3-s pressure control breath delivered once per minute at 30 cmH2O. Standardized protocols will guide ventilation settings, switch back to controlled ventilation, use of rescue treatments, performance of spontaneous breathing trial, extubation and reintubation. The primary endpoint of the study will be to verify the feasibility of PSV + sigh evaluated through reduction of failure to remain on assisted ventilation during the first 28 days in the PSV + sigh group versus standard PSV (15 vs. 22%). Failure will be defined by switch back to controlled ventilation for more than 24 h or use of rescue treatments or reintubation within 48 h from elective extubation. Setting the power to 80% and first-risk order to 5%, the computed size of the trial is 129 patients per arm. DISCUSSION: PROTECTION is a pilot randomized controlled trial testing the feasibility of adding sigh to PSV. If positive, it will provide physicians with an effective addition to standard PSV for lung protection, able to reduce failure of assisted ventilation. PROTECTION will provide the basis for a future larger trial aimed at verifying the impact of PSV + sigh on 28-day survival and ventilator-free days. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03201263 . Registered on 28 June 2017.

Current adoption of lung ultrasound in Intensive Care Units: an Italian multi-center survey.

BACKGROUND: Lung ultrasound (LUS) is a useful tool for assessing lung status in critically ill patients, but is not widely applied in intensive care units (ICUs). The aim of this study was to investigate the use of LUS in Italian ICUs. METHODS: A questionnaire was distributed to 116 ICU representatives belonging to the Italian GiViTI network, participating in a national project on continuous quality of care assessment. The answers to the questionnaire were analyzed with the data collected in the course of said project. RESULTS: 87 ICUs took part in the study. LUS was performed in 94.3% of them, generally by an internal intensivist. The mean number of tests per bed per week was 0.97 (SD, 1.0). A standardized reporting format was present in only 11% of ICUs. LUS was generally used to investigate known or suspected diseases and as a screening tool in only 10%. The number of testes per bed per week was inversely correlated to the number of beds per physician (P<0.001) and to the provider performing the LUS (P<0.001), but not to other structural, organizational or performance data. CONCLUSIONS: LUS is performed in the majority of ICUs and is generally used to investigate known or suspected diseases. Frequency of use appears to be low and related to selected organizational factors. There is generally no standardized format for reporting LUS findings.

Second-opinion stress tele-echocardiography for the Adonhers (Aged donor heart rescue by stress echo) project.

BACKGROUND: To resolve the current shortage of donor hearts, we established the Adonhers protocol. An upward shift of the donor age cut-off limit (from the present 55 to 65 years) is acceptable if a stress echo screening on the candidate donor heart is normal. This study aimed to verify feasibility of a "second opinion" of digitally transferred images of stress echo results to minimize technical variability in selection of aged donor hearts for heart transplant. METHODS: The informatics infrastructure was created for a core lab reading with a second opinion from the Pisa stress echo lab. To test the system, simulation standard stress echo cineloops were sent digitally from 5 peripheral labs to the central core lab.Starting January 2009, real marginal donor stress echos were sent via internet to the central core echo lab, Pisa, for a second opinion before heart transplant. RESULTS: In the simulation protocol, 30 dipyridamole stress echocardiograms were sent from the five peripheral echo labs to the central core lab in Pisa. Both the echo images and reports were correctly uploaded in the web system and sent to the core echo lab; the second opinion evaluation was obtained in all cases (100% feasibility). In the transplant protocol, eight donor cases were sent to the Pisa core lab for the second opinion protocol, and six of them were transplanted in marginal recipients. CONCLUSIONS: Second-Opinion Stress Tele-Echocardiography can effectively be performed in a network aimed to safely expand the heart donor pool for heart transplant.

Peribulbar anesthesia: a percutaneous single injection technique with a small volume of anesthetic.

We evaluated the efficacy and safety of a single injection technique with a small volume of anesthetic for ocular peribulbar anesthesia. We included 857 patients undergoing various ophthalmic procedures. Anesthesia consisted of a medial percutaneous injection of 5-6.5 mL of 2% lidocaine. At 2 min 85.6% of the patients had a motor block of at least 50% and at 5 min 78.6% had a motor block >80%. After 5 min 100% of the patients had adequate surgical anesthesia. There were no serious block-related complications. The described technique is a simple and satisfactory alternative to the classical techniques.