Advancements in understanding the mechanisms of lung-kidney crosstalk.

This narrative review delves into the intricate interplay between the lungs and the kidneys, with a focus on elucidating the pathogenesis of diseases influenced by immunological factors, acid-base regulation, and blood gas disturbances, as well as assessing the effects of various therapeutic modalities on these interactions. Key disorders, such as anti-glomerular basement membrane (anti-GBM) disease, the syndrome of inappropriate antidiuretic hormone secretion (SIADH), and Anti-neutrophil Cytoplasmic Antibodies (ANCA) associated vasculitis (AAV), are also examined to shed light on their underlying mechanisms. This review also explores the relationship between acute respiratory distress syndrome (ARDS) and acute kidney injury (AKI), emphasizing how inflammatory mediators can lead to systemic damage and impact multiple organs. In ARDS, fluid overload exacerbates pulmonary edema, while imbalances in blood volume, such as hypovolemia or hypervolemia, can precipitate renal dysfunction. The review highlights how mechanical ventilation strategies can compromise renal blood flow, trigger systemic inflammation, and induce hemodynamic and neurohormonal alterations, all contributing to lung and kidney damage. The impact of extracorporeal membrane oxygenation (ECMO) on lung-kidney interactions is evaluated, highlighting its role in severe respiratory failure and its renal implications. Emerging therapies, such as mesenchymal stem cells and extracellular vesicles, are discussed as promising avenues to mitigate organ damage and enhance outcomes in critically ill patients. Overall, this review offers a nuanced exploration of lung-kidney dynamics, bridging historical insights with contemporary perspectives. It underscores the clinical significance of these interactions in critically ill patients and advocates for integrated management approaches to optimize patient outcomes.

Predicting short-term outcomes in brain-injured patients: a comprehensive approach with transcranial Doppler and intracranial compliance assessment.

Neurocritical patients frequently exhibit abnormalities in cerebral hemodynamics (CH) and/or intracranial compliance (ICC), all of which significantly impact their clinical outcomes. Transcranial Doppler (TCD) and the cranial micro-deformation sensor (B4C) are valuable techniques for assessing CH and ICC, respectively. However, there is a scarcity of data regarding the predictive value of these techniques in determining patient outcomes. We prospectively included neurocritical patients undergoing intracranial pressure (ICP) monitoring within the first 5 days of hospital admission for TCD and B4C assessments. Comprehensive clinical data were collected alongside parameters obtained from TCD (including the estimated ICP [eICP] and estimated cerebral perfusion pressure [eCPP]) and B4C (measured as the P2/P1 ratio). These parameters were evaluated individually as well as in combination. The short-term outcomes (STO) of interest were the therapy intensity levels (TIL) for ICP management recommended by the Seattle International Brain Injury Consensus Conference, as TIL 0 (STO 1), TIL 1-3 (STO 2) and death (STO 3), at the seventh day after last data collection. The dataset was randomly separated in test and training samples, area under the curve (AUC) was used to represent the noninvasive techniques ability on the STO prediction and association with ICP. A total of 98 patients were included, with 67% having experienced severe traumatic brain injury and 15% subarachnoid hemorrhage, whilst the remaining patients had ischemic or hemorrhagic stroke. ICP, P2/P1, and eCPP demonstrated the highest ability to predict early mortality (p = 0.02, p = 0.02, and p = 0.006, respectively). P2/P1 was the only parameter significant for the prediction of STO 1 (p = 0.03). Combining B4C and TCD parameters, the highest AUC was 0.85 to predict death (STO 3), using P2/P1 + eCPP, whereas AUC was 0.72 to identify ICP > 20 mmHg using P2/P1 + eICP. The combined noninvasive neuromonitoring approach using eCPP and P2/P1 ratio demonstrated improved performance in predicting outcomes during the early phase after acute brain injury. The correlation with intracranial hypertension was moderate, by means of eICP and P2/P1 ratio. These results support the need for interpretation of this information in the ICU and warrant further investigations for the definition of therapy strategies using ancillary tests.

A Comprehensive Perspective on Intracranial Pressure Monitoring and Individualized Management in Neurocritical Care: Results of a Survey with Global Experts.

BACKGROUND: Numerous trials have addressed intracranial pressure (ICP) management in neurocritical care. However, identifying its harmful thresholds and controlling ICP remain challenging in terms of improving outcomes. Evidence suggests that an individualized approach is necessary for establishing tolerance limits for ICP, incorporating factors such as ICP waveform (ICPW) or pulse morphology along with additional data provided by other invasive (e.g., brain oximetry) and noninvasive monitoring (NIM) methods (e.g., transcranial Doppler, optic nerve sheath diameter ultrasound, and pupillometry). This study aims to assess current ICP monitoring practices among experienced clinicians and explore whether guidelines should incorporate ancillary parameters from NIM and ICPW in future updates. METHODS: We conducted a survey among experienced professionals involved in researching and managing patients with severe injury across low-middle-income countries (LMICs) and high-income countries (HICs). We sought their insights on ICP monitoring, particularly focusing on the impact of NIM and ICPW in various clinical scenarios. RESULTS: From October to December 2023, 109 professionals from the Americas and Europe participated in the survey, evenly distributed between LMIC and HIC. When ICP ranged from 22 to 25 mm Hg, 62.3% of respondents were open to considering additional information, such as ICPW and other monitoring techniques, before adjusting therapy intensity levels. Moreover, 77% of respondents were inclined to reassess patients with ICP in the 18-22 mm Hg range, potentially escalating therapy intensity levels with the support of ICPW and NIM. Differences emerged between LMIC and HIC participants, with more LMIC respondents preferring arterial blood pressure transducer leveling at the heart and endorsing the use of NIM techniques and ICPW as ancillary information. CONCLUSIONS: Experienced clinicians tend to personalize ICP management, emphasizing the importance of considering various monitoring techniques. ICPW and noninvasive techniques, particularly in LMIC settings, warrant further exploration and could potentially enhance individualized patient care. The study suggests updating guidelines to include these additional components for a more personalized approach to ICP management.

Comparison between high-flow nasal oxygen (HFNO) alternated with non-invasive ventilation (NIV) and HFNO and NIV alone in patients with COVID-19: a retrospective cohort study.

BACKGROUND: Non-invasive respiratory support (conventional oxygen therapy [COT], non-invasive ventilation [NIV], high-flow nasal oxygen [HFNO], and NIV alternated with HFNO [NIV + HFNO] may reduce the need for invasive mechanical ventilation (IMV) in patients with COVID-19. The outcome of patients treated non-invasively depends on clinical severity at admission. We assessed the need for IMV according to NIV, HFNO, and NIV + HFNO in patients with COVID-19 according to disease severity and evaluated in-hospital survival rates and hospital and intensive care unit (ICU) lengths of stay. METHODS: This cohort study was conducted using data collected between March 2020 and July 2021. Patients ≥ 18 years admitted to the ICU with a diagnosis of COVID-19 were included. Patients hospitalized for < 3 days, receiving therapy (COT, NIV, HFNO, or NIV + HFNO) for < 48 h, pregnant, and with no primary outcome data were excluded. The COT group was used as reference for multivariate Cox regression model adjustment. RESULTS: Of 1371 patients screened, 958 were eligible: 692 (72.2%) on COT, 92 (9.6%) on NIV, 31 (3.2%) on HFNO, and 143 (14.9%) on NIV + HFNO. The results for the patients in each group were as follows: median age (interquartile range): NIV (64 [49-79] years), HFNO (62 [55-70] years), NIV + HFNO (62 [48-72] years) (p = 0.615); heart failure: NIV (54.5%), HFNO (36.3%), NIV + HFNO (9%) (p = 0.003); diabetes mellitus: HFNO (17.6%), NIV + HFNO (44.7%) (p = 0.048). > 50% lung damage on chest computed tomography (CT): NIV (13.3%), HFNO (15%), NIV + HFNO (71.6%) (p = 0.038); SpO2/FiO2: NIV (271 [118-365] mmHg), HFNO (317 [254-420] mmHg), NIV + HFNO (229 [102-317] mmHg) (p = 0.001); rate of IMV: NIV (26.1%, p = 0.002), HFNO (22.6%, p = 0.023), NIV + HFNO (46.8%); survival rate: HFNO (83.9%), NIV + HFNO (63.6%) (p = 0.027); ICU length of stay: NIV (8.5 [5-14] days), NIV + HFNO (15 [10-25] days (p < 0.001); hospital length of stay: NIV (13 [10-21] days), NIV + HFNO (20 [15-30] days) (p < 0.001). After adjusting for comorbidities, chest CT score and SpO2/FiO2, the risk of IMV in patients on NIV + HFNO remained high (hazard ratio, 1.88; 95% confidence interval, 1.17-3.04). CONCLUSIONS: In patients with COVID-19, NIV alternating with HFNO was associated with a higher rate of IMV independent of the presence of comorbidities, chest CT score and SpO2/FiO2. Trial registration ClinicalTrials.gov identifier: NCT05579080.

Quantitative Pupillometry for Intracranial Pressure (ICP) Monitoring in Traumatic Brain Injury: A Scoping Review.

The neurological examination has remained key for the detection of worsening in neurocritical care patients, particularly after traumatic brain injury (TBI). New-onset, unreactive anisocoria frequently occurs in such situations, triggering aggressive diagnostic and therapeutic measures to address life-threatening elevations in intracranial pressure (ICP). As such, the field needs objective, unbiased, portable, and reliable methods for quickly assessing such pupillary changes. In this area, quantitative pupillometry (QP) proves promising, leveraging the analysis of different pupillary variables to indirectly estimate ICP. Thus, this scoping review seeks to describe the existing evidence for the use of QP in estimating ICP in adult patients with TBI as compared with invasive methods, which are considered the standard practice. This review was conducted in accordance with the Joanna Briggs Institute methodology for scoping reviews, with a main search of PubMed and EMBASE. The search was limited to studies of adult patients with TBI published in any language between 2012 and 2022. Eight studies were included for analysis, with the vast majority being prospective studies conducted in high-income countries. Among QP variables, serial rather than isolated measurements of neurologic pupillary index, constriction velocity, and maximal constriction velocity demonstrated the best correlation with invasive ICP measurement values, particularly in predicting refractory intracranial hypertension. Neurologic pupillary index and ICP also showed an inverse relationship when trends were simultaneously compared. As such, QP, when used repetitively, seems to be a promising tool for noninvasive ICP monitoring in patients with TBI, especially when used in conjunction with other clinical and neuromonitoring data.

ICP wave morphology as a screening test to exclude intracranial hypertension in brain-injured patients: a non-invasive perspective.

Intracranial hypertension (IH) is a life-threating condition especially for the brain injured patient. In such cases, an external ventricular drain (EVD) or an intraparenchymal bolt are the conventional gold standard for intracranial pressure (ICPi) monitoring. However, these techniques have several limitations. Therefore, identifying an ideal screening method for IH is important to avoid the unnecessary placement of ICPi and expedite its introduction in patients who require it. A potential screening tool is the ICP wave morphology (ICPW) which changes according to the intracranial volume-pressure curve. Specifically, the P2/P1 ratio of the ICPW has shown promise as a triage test to indicate normal ICP. In this study, we propose evaluating the noninvasive ICPW (nICPW-B4C sensor) as a screening method for ICPi monitoring in patients with moderate to high probability of IH. This is a retrospective analysis of a prospective, multicenter study that recruited adult patients requiring ICPi monitoring from both Federal University of São Paulo and University of São Paulo Medical School Hospitals. ICPi values and the nICPW parameters were obtained from both the invasive and the noninvasive methods simultaneously 5 min after the closure of the EVD drainage. ICP assessment was performed using a catheter inserted into the ventricle and connected to a pressure transducer and a drainage system. The B4C sensor was positioned on the patient's scalp without the need for trichotomy, surgical incision or trepanation, and the morphology of the ICP waves acquired through a strain sensor that can detect and monitor skull bone deformations caused by changes in ICP. All patients were monitored using this noninvasive system for at least 10 min per session. The area under the curve (AUC) was used to describe discriminatory power of the P2/P1 ratio for IH, with emphasis in the Negative Predictive value (NPV), based on the Youden index, and the negative likelihood ratio [LR-]. Recruitment occurred from August 2017 to March 2020. A total of 69 patients fulfilled inclusion and exclusion criteria in the two centers and a total of 111 monitorizations were performed. The mean P2/P1 ratio value in the sample was 1.12. The mean P2/P1 value in the no IH population was 1.01 meanwhile in the IH population was 1.32 (p < 0.01). The best Youden index for the mean P2/P1 ratio was with a cut-off value of 1.13 showing a sensitivity of 93%, specificity of 60%, and a NPV of 97%, as well as an AUC of 0.83 to predict IH. With the 1.13 cut-off value for P2/P1 ratio, the LR- for IH was 0.11, corresponding to a strong performance in ruling out the condition (IH), with an approximate 45% reduction in condition probability after a negative test (ICPW). To conclude, the P2/P1 ratio of the noninvasive ICP waveform showed in this study a high Negative Predictive Value and Likelihood Ratio in different acute neurological conditions to rule out IH. As a result, this parameter may be beneficial in situations where invasive methods are not feasible or unavailable and to screen high-risk patients for potential invasive ICP monitoring.Trial registration: At clinicaltrials.gov under numbers NCT05121155 (Registered 16 November 2021-retrospectively registered) and NCT03144219 (Registered 30 September 2022-retrospectively registered).

Non-Invasive Methods for Intracranial Pressure Monitoring in Traumatic Brain Injury Using Transcranial Doppler: A Scoping Review.

Intracranial pressure (ICP) monitoring is necessary for managing patients with traumatic brain injury (TBI). Although gold-standard methods include intraventricular or intraparenchymal transducers, these systems cannot be used in patients with coagulopathies or in those who are at high risk of catheter-related infections, nor can they be used in resource-constrained settings. Therefore, a non-invasive modality that is more widely available, cost effective, and safe would have tremendous impact. Among such non-invasive choices, transcranial Doppler (TCD) provides indirect ICP estimates through waveform analysis of cerebral hemodynamic changes. The objective of this scoping review is to describe the existing evidence for the use of TCD-derived methods in estimating ICP in adult TBI patients as compared with gold-standard invasive methods. This review was conducted in accordance with the Joanna Briggs Institute methodology for scoping reviews, with a main search of PubMed and Embase. The search was limited to studies conducted in adult TBI patients published in any language between 2012 and 2022. Twenty-two studies were included for analysis, with most being prospective studies conducted in high-income countries. TCD-derived non-invasive ICP (nICP) methods are either mathematical or non-mathematical, with the former having slightly better correlation with invasive methods, especially when using time-trending ICP dynamics over one-time estimated values. Nevertheless, mathematical methods are associated with greater cost and complexity in their application. Formula-based methods showed promise in excluding elevated ICP, exhibiting a high negative predictive value. Therefore, TCD-derived methods could be useful in assessing ICP changes instead of absolute ICP values for high-risk patients, especially in low-resource settings.

Using Optic Nerve Sheath Diameter for Intracranial Pressure (ICP) Monitoring in Traumatic Brain Injury: A Scoping Review.

INTRODUCTION: Neuromonitoring represents a cornerstone in the comprehensive management of patients with traumatic brain injury (TBI), allowing for early detection of complications such as increased intracranial pressure (ICP) [1]. This has led to a search for noninvasive modalities that are reliable and deployable at bedside. Among these, ultrasonographic optic nerve sheath diameter (ONSD) measurement is a strong contender, estimating ICP by quantifying the distension of the optic nerve at higher ICP values. Thus, this scoping review seeks to describe the existing evidence for the use of ONSD in estimating ICP in adult TBI patients as compared to gold-standard invasive methods. MATERIALS AND METHODS: This review was conducted in accordance with the Joanna Briggs Institute methodology for scoping reviews, with a main search of PubMed and EMBASE. The search was limited to studies of adult patients with TBI published in any language between 2012 and 2022. Sixteen studies were included for analysis, with all studies conducted in high-income countries. RESULTS: All of the studies reviewed measured ONSD using the same probe frequency. In most studies, the marker position for ONSD measurement was initially 3 mm behind the globe, retina, or papilla. A few studies utilized additional parameters such as the ONSD/ETD (eyeball transverse diameter) ratio or ODE (optic disc elevation), which also exhibit high sensitivity and reliability. CONCLUSION: Overall, ONSD exhibits great test accuracy and has a strong, almost linear correlation with invasive methods. Thus, ONSD should be considered one of the most effective noninvasive techniques for ICP estimation in TBI patients.

Pressure-support compared with pressure-controlled ventilation mitigates lung and brain injury in experimental acute ischemic stroke in rats.

BACKGROUND: We aimed to evaluate the pulmonary and cerebral effects of low-tidal volume ventilation in pressure-support (PSV) and pressure-controlled (PCV) modes at two PEEP levels in acute ischemic stroke (AIS). METHODS: In this randomized experimental study, AIS was induced by thermocoagulation in 30 healthy male Wistar rats. After 24 h, AIS animals were randomly assigned to PSV or PCV with VT = 6 mL/kg and PEEP = 2 cmH2O (PSV-PEEP2 and PCV-PEEP2) or PEEP = 5 cmH2O (PSV-PEEP5 and PCV-PEEP5) for 2 h. Lung mechanics, arterial blood gases, and echocardiography were evaluated before and after the experiment. Lungs and brain tissue were removed for histologic and molecular biology analysis. The primary endpoint was diffuse alveolar damage (DAD) score; secondary endpoints included brain histology and brain and lung molecular biology markers. RESULTS: In lungs, DAD was lower with PSV-PEEP5 than PCV-PEEP5 (p < 0.001); interleukin (IL)-1ß was lower with PSV-PEEP2 than PCV-PEEP2 (p = 0.016) and PSV-PEEP5 than PCV-PEEP5 (p = 0.046); zonula occludens-1 (ZO-1) was lower in PCV-PEEP5 than PCV-PEEP2 (p = 0.042). In brain, necrosis, hemorrhage, neuropil edema, and CD45 + microglia were lower in PSV than PCV animals at PEEP = 2 cmH2O (p = 0.036, p = 0.025, p = 0.018, p = 0.011, respectively) and PEEP = 5 cmH2O (p = 0.003, p = 0.003, p = 0.007, p = 0.003, respectively); IL-1ß was lower while ZO-1 was higher in PSV-PEEP2 than PCV-PEEP2 (p = 0.009, p = 0.007, respectively), suggesting blood-brain barrier integrity. Claudin-5 was higher in PSV-PEEP2 than PSV-PEEP5 (p = 0.036). CONCLUSION: In experimental AIS, PSV compared with PCV reduced lung and brain injury. Lung ZO-1 reduced in PCV with PEEP = 2 versus PEEP = 5 cmH2O, while brain claudin-5 increased in PSV with PEEP = 2 versus PEEP = 5 cmH2O.

Dexmedetomidine compared to low-dose ketamine better protected not only the brain but also the lungs in acute ischemic stroke.

BACKGROUND: Dexmedetomidine (DEX) and low-dose ketamine (KET) present neuroprotective effects in acute ischemic stroke (AIS); however, to date, no studies have evaluated which has better protective effects not only on the brain but also lungs in AIS. METHODS: AIS-induced Wistar rats (390 ± 30 g) were randomized after 24-h, receiving dexmedetomidine (STROKE-DEX, n = 10) or low-dose S(+)-ketamine (STROKE-KET, n = 10). After 1-h protective ventilation, perilesional brain tissue and lungs were removed for histologic and molecular biology analysis. STROKE animals (n = 5), receiving sodium thiopental but not ventilated, had brain and lungs removed for molecular biology analysis. Effects of DEX and KET mean plasma concentrations on alveolar macrophages, neutrophils, and lung endothelial cells, extracted primarily 24-h after AIS, were evaluated. RESULTS: In perilesional brain tissue, apoptosis did not differ between groups. In STROKE-DEX, compared to STROKE-KET, tumor necrosis factor (TNF)-α and vascular cell adhesion molecule-1 (VCAM-1) expressions were reduced, but no changes in nuclear factor erythroid 2-related factor-2 (Nrf2) and super oxide dismutase (SOD)-1 were observed. In lungs, TNF-α and VCAM-1 were reduced, whereas Nrf2 and SOD-1 were increased in STROKE-DEX. In alveolar macrophages, TNF-α and inducible nitric oxide synthase (M1 macrophage phenotype) were lower and arginase and transforming growth factor-ß (M2 macrophage phenotype) higher in STROKE-DEX. In lung neutrophils, CXC chemokine receptors (CXCR2 and CXCR4) were higher in STROKE-DEX. In lung endothelial cells, E-selectin and VCAM-1 were lower in STROKE-DEX. CONCLUSIONS: In the current AIS model, dexmedetomidine compared to low-dose ketamine reduced inflammation and endothelial cell damage in both brain and lung, suggesting greater protection.

Fluid management strategies and their interaction with mechanical ventilation: from experimental studies to clinical practice.

Patients on mechanical ventilation may receive intravenous fluids via restrictive or liberal fluid management. A clear and objective differentiation between restrictive and liberal fluid management strategies is lacking in the literature. The liberal approach has been described as involving fluid rates ranging from 1.2 to 12 times higher than the restrictive approach. A restrictive fluid management may lead to hypoperfusion and distal organ damage, and a liberal fluid strategy may result in endothelial shear stress and glycocalyx damage, cardiovascular complications, lung edema, and distal organ dysfunction. The association between fluid and mechanical ventilation strategies and how they interact toward ventilator-induced lung injury (VILI) could potentiate the damage. For instance, the combination of a liberal fluids and pressure-support ventilation, but not pressure control ventilation, may lead to further lung damage in experimental models of acute lung injury. Moreover, under liberal fluid management, the application of high positive end-expiratory pressure (PEEP) or an abrupt decrease in PEEP yielded higher endothelial cell damage in the lungs. Nevertheless, the translational aspects of these findings are scarce. The aim of this narrative review is to provide better understanding of the interaction between different fluid and ventilation strategies and how these interactions may affect lung and distal organs. The weaning phase of mechanical ventilation and the deresuscitation phase are not explored in this review.

New and personalized ventilatory strategies in patients with COVID-19.

Coronavirus disease (COVID-19) is caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) virus and may lead to severe respiratory failure and the need for mechanical ventilation (MV). At hospital admission, patients can present with severe hypoxemia and dyspnea requiring increasingly aggressive MV strategies according to the clinical severity: noninvasive respiratory support (NRS), MV, and the use of rescue strategies such as extracorporeal membrane oxygenation (ECMO). Among NRS strategies, new tools have been adopted for critically ill patients, with advantages and disadvantages that need to be further elucidated. Advances in the field of lung imaging have allowed better understanding of the disease, not only the pathophysiology of COVID-19 but also the consequences of ventilatory strategies. In cases of refractory hypoxemia, the use of ECMO has been advocated and knowledge on handling and how to personalize strategies have increased during the pandemic. The aims of the present review are to: (1) discuss the evidence on different devices and strategies under NRS; (2) discuss new and personalized management under MV based on the pathophysiology of COVID-19; and (3) contextualize the use of rescue strategies such as ECMO in critically ill patients with COVID-19.

"THE MANTLE" bundle for minimizing cerebral hypoxia in severe traumatic brain injury.

To ensure neuronal survival after severe traumatic brain injury, oxygen supply is essential. Cerebral tissue oxygenation represents the balance between oxygen supply and consumption, largely reflecting the adequacy of cerebral perfusion. Multiple physiological parameters determine the oxygen delivered to the brain, including blood pressure, hemoglobin level, systemic oxygenation, microcirculation and many factors are involved in the delivery of oxygen to its final recipient, through the respiratory chain. Brain tissue hypoxia occurs when the supply of oxygen is not adequate or when for some reasons it cannot be used at the cellular level. The causes of hypoxia are variable and can be analyzed pathophysiologically following "the oxygen route." The current trend is precision medicine, individualized and therapeutically directed to the pathophysiology of specific brain damage; however, this requires the availability of multimodal monitoring. For this purpose, we developed the acronym "THE MANTLE," a bundle of therapeutical interventions, which covers and protects the brain, optimizing the components of the oxygen transport system from ambient air to the mitochondria.

High flow nasal oxygen and awake prone positioning - Two allies against COVID-19: A systematic review.

INTRODUCTION: Severe acute respiratory distress syndrome coronavirus disease-2 (SARS-CoV-2) can lead to acute hypoxemic respiratory failure (AHRF) with possible multisystemic involvement. Ventilation/perfusion mismatch and shunt increase are critical determinants of hypoxemia. Understanding hypoxemia and the mechanisms involved in its genesis is essential to determine the optimal therapeutic strategy. High flow nasal oxygen (HFNO) and awake prone positioning (APP) in patients with COVID-19 AHRF showed promising benefits. The aim of this systematic review was to depict current situation around the combined use of HFNO and APP in patients with COVID-19 AHRF. Particularly, to investigate and report the pathophysiological rationale for adopting this strategy and to evaluate the (1) criteria for initiation, (2) timing, monitoring and discontinuation, and to assess the (3) impact of HFNO/ APP on outcome. METHODS: We performed a systematic search collecting the articles present in PubMed, Scopus, EMBASE, and Cochrane databases with the following keywords: COVID-19 pneumonia, high flow nasal oxygen, awake prone position ventilation. RESULTS: Thirteen studies displayed inclusion criteria and were included, accounting for 1242 patients who received HFNO/ APP. The combination of HFNO/ APP has an encouraging pathophysiological rationale for implementing this technique. The recognition of patients who can benefit from HFNO/ APP is difficult and there are no validated protocols to start, monitoring, and discontinue HFNO/ APP therapy. The most used method to monitor the efficacy and failure of this combined technique are oxygenation indexes, but discontinuation techniques are inconsistently and poorly described limiting possible generatability. Finally, this technique provided no clear benefits on outcome. CONCLUSIONS: Our systematic search provided positive feedbacks for improving the utilization of this combination technique, although we still need further investigation about methods to guide timing, management, and discontinuation, and to assess the intervention effect on outcome.

Noninvasive intracranial pressure waveforms for estimation of intracranial hypertension and outcome prediction in acute brain-injured patients.

Analysis of intracranial pressure waveforms (ICPW) provides information on intracranial compliance. We aimed to assess the correlation between noninvasive ICPW (NICPW) and invasively measured intracranial pressure (ICP) and to assess the NICPW prognostic value in this population. In this cohort, acute brain-injured (ABI) patients were included within 5 days from admission in six Intensive Care Units. Mean ICP (mICP) values and the P2/P1 ratio derived from NICPW were analyzed and correlated with outcome, which was defined as: (a) early death (ED); survivors on spontaneous breathing (SB) or survivors on mechanical ventilation (MV) at 7 days from inclusion. Intracranial hypertension (IHT) was defined by ICP > 20 mmHg. A total of 72 patients were included (mean age 39, 68% TBI). mICP and P2/P1 values were significantly correlated (r = 0.49, p < 0.001). P2/P1 ratio was significantly higher in patients with IHT and had an area under the receiving operator curve (AUROC) to predict IHT of 0.88 (95% CI 0.78-0.98). mICP and P2/P1 ratio was also significantly higher for ED group (n = 10) than the other groups. The AUROC of P2/P1 to predict ED was 0.71 [95% CI 0.53-0.87], and the threshold P2/P1 > 1.2 showed a sensitivity of 60% [95% CI 31-83%] and a specificity of 69% [95% CI 57-79%]. Similar results were observed when decompressive craniectomy patients were excluded. In this study, P2/P1 derived from noninvasive ICPW assessment was well correlated with IHT. This information seems to be as associated with ABI patients outcomes as ICP.Trial registration: NCT03144219, Registered 01 May 2017 Retrospectively registered, https://www.clinicaltrials.gov/ct2/show/NCT03144219 .

POCUS, how can we include the brain? An overview.

Point-of-care ultrasound (POCUS) is an essential tool to assess and manage different pathologies in the intensive care unit, and many protocols have been proposed for its application in critical care literature. However, the brain has been overlooked in these protocols.Brain ultrasonography (BU) is easily available, and it allows a goal-directed approach thanks to its repeatability and immediate interpretation and provides a quick management and real time assessment of patients' conditions. Based on recent studies, the increasing interest from intensivists, and the undeniable benefits of ultrasound, the main goal of this overview is to describe the main evidence and progresses in the incorporation of BU into the POCUS approach in the daily practice, and thus becoming POCUS-BU. This integration would allow a noninvasive global assessment to entail an integrated analysis of the critical care patients.