Modelling midline shift and ventricle collapse in cerebral oedema following acute ischaemic stroke.

In ischaemic stroke, a large reduction in blood supply can lead to the breakdown of the blood-brain barrier and to cerebral oedema after reperfusion therapy. The resulting fluid accumulation in the brain may contribute to a significant rise in intracranial pressure (ICP) and tissue deformation. Changes in the level of ICP are essential for clinical decision-making and therapeutic strategies. However, the measurement of ICP is constrained by clinical techniques and obtaining the exact values of the ICP has proven challenging. In this study, we propose the first computational model for the simulation of cerebral oedema following acute ischaemic stroke for the investigation of ICP and midline shift (MLS) relationship. The model consists of three components for the simulation of healthy blood flow, occluded blood flow and oedema, respectively. The healthy and occluded blood flow components are utilized to obtain oedema core geometry and then imported into the oedema model for the simulation of oedema growth. The simulation results of the model are compared with clinical data from 97 traumatic brain injury patients for the validation of major model parameters. Midline shift has been widely used for the diagnosis, clinical decision-making, and prognosis of oedema patients. Therefore, we focus on quantifying the relationship between ICP and midline shift (MLS) and identify the factors that can affect the ICP-MLS relationship. Three major factors are investigated, including the brain geometry, blood-brain barrier damage severity and the types of oedema (including rare types of oedema). Meanwhile, the two major types (stress and tension/compression) of mechanical brain damage are also presented and the differences in the stress, tension, and compression between the intraparenchymal and periventricular regions are discussed. This work helps to predict ICP precisely and therefore provides improved clinical guidance for the treatment of brain oedema.

Targeted temperature control following traumatic brain injury: ESICM/NACCS best practice consensus recommendations.

AIMS AND SCOPE: The aim of this panel was to develop consensus recommendations on targeted temperature control (TTC) in patients with severe traumatic brain injury (TBI) and in patients with moderate TBI who deteriorate and require admission to the intensive care unit for intracranial pressure (ICP) management. METHODS: A group of 18 international neuro-intensive care experts in the acute management of TBI participated in a modified Delphi process. An online anonymised survey based on a systematic literature review was completed ahead of the meeting, before the group convened to explore the level of consensus on TTC following TBI. Outputs from the meeting were combined into a further anonymous online survey round to finalise recommendations. Thresholds of ≥ 16 out of 18 panel members in agreement (≥ 88%) for strong consensus and ≥ 14 out of 18 (≥ 78%) for moderate consensus were prospectively set for all statements. RESULTS: Strong consensus was reached on TTC being essential for high-quality TBI care. It was recommended that temperature should be monitored continuously, and that fever should be promptly identified and managed in patients perceived to be at risk of secondary brain injury. Controlled normothermia (36.0-37.5 °C) was strongly recommended as a therapeutic option to be considered in tier 1 and 2 of the Seattle International Severe Traumatic Brain Injury Consensus Conference ICP management protocol. Temperature control targets should be individualised based on the perceived risk of secondary brain injury and fever aetiology. CONCLUSIONS: Based on a modified Delphi expert consensus process, this report aims to inform on best practices for TTC delivery for patients following TBI, and to highlight areas of need for further research to improve clinical guidelines in this setting.

Effects of mechanical ventilation on the interstitial extracellular matrix in healthy lungs and lungs affected by acute respiratory distress syndrome: a narrative review.

BACKGROUND: Mechanical ventilation, a lifesaving intervention in critical care, can lead to damage in the extracellular matrix (ECM), triggering inflammation and ventilator-induced lung injury (VILI), particularly in conditions such as acute respiratory distress syndrome (ARDS). This review discusses the detailed structure of the ECM in healthy and ARDS-affected lungs under mechanical ventilation, aiming to bridge the gap between experimental insights and clinical practice by offering a thorough understanding of lung ECM organization and the dynamics of its alteration during mechanical ventilation. MAIN TEXT: Focusing on the clinical implications, we explore the potential of precise interventions targeting the ECM and cellular signaling pathways to mitigate lung damage, reduce inflammation, and ultimately improve outcomes for critically ill patients. By analyzing a range of experimental studies and clinical papers, particular attention is paid to the roles of matrix metalloproteinases (MMPs), integrins, and other molecules in ECM damage and VILI. This synthesis not only sheds light on the structural changes induced by mechanical stress but also underscores the importance of cellular responses such as inflammation, fibrosis, and excessive activation of MMPs. CONCLUSIONS: This review emphasizes the significance of mechanical cues transduced by integrins and their impact on cellular behavior during ventilation, offering insights into the complex interactions between mechanical ventilation, ECM damage, and cellular signaling. By understanding these mechanisms, healthcare professionals in critical care can anticipate the consequences of mechanical ventilation and use targeted strategies to prevent or minimize ECM damage, ultimately leading to better patient management and outcomes in critical care settings.

Contemporary management of aneurysmal subarachnoid haemorrhage. An update for the intensivist.

Aneurysmal subarachnoid haemorrhage (aSAH) is a rare yet profoundly debilitating condition associated with high global case fatality and morbidity rates. The key determinants of functional outcome include early brain injury, rebleeding of the ruptured aneurysm and delayed cerebral ischaemia. The only effective way to reduce the risk of rebleeding is to secure the ruptured aneurysm quickly. Prompt diagnosis, transfer to specialized centers, and meticulous management in the intensive care unit (ICU) significantly improved the prognosis of aSAH. Recently, multimodality monitoring with specific interventions to correct pathophysiological imbalances has been proposed. Vigilance extends beyond intracranial concerns to encompass systemic respiratory and haemodynamic monitoring, as derangements in these systems can precipitate secondary brain damage. Challenges persist in treating aSAH patients, exacerbated by a paucity of robust clinical evidence, with many interventions showing no benefit when tested in rigorous clinical trials. Given the growing body of literature in this field and the issuance of contemporary guidelines, our objective is to furnish an updated review of essential principles of ICU management for this patient population. Our review will discuss the epidemiology, initial stabilization, treatment strategies, long-term prognostic factors, the identification and management of post-aSAH complications. We aim to offer practical clinical guidance to intensivists, grounded in current evidence and expert clinical experience, while adhering to a concise format.

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.

The time constant of the cerebral arterial bed: exploring age-related implications.

The time constant of the cerebral arterial bed (τ) represents an estimation of the  transit time of flow from the point of insonation at the level of the middle cerebral artery to the arteriolar-capillary boundary, during a cardiac cycle. This study assessed differences in τ among healthy volunteers across different age groups. Simultaneous recordings of transcranial Doppler cerebral blood flow velocity (CBFV) and arterial blood pressure (ABP) were performed on two groups: young volunteers (below 30 years of age), and older volunteers (above 40 years of age). τ was estimated using mathematical transformation of ABP and CBFV pulse waveforms. 77 healthy volunteers [52 in the young group, and 25 in the old group] were included. Pulse amplitude of ABP was higher [16.7 (14.6-19.4) mmHg] in older volunteers as compared to younger ones [12.5 (10.9-14.4) mm Hg; p < 0.001]. CBFV was lower in older volunteers [59 (50-66) cm/s] as compared to younger ones [72 (63-78) cm/s p < 0.001]. τ was longer in the younger volunteers [217 (168-237) ms] as compared to the older volunteers [183 (149-211) ms; p = 0.004]. τ significantly decreased with age (rS = - 0.27; p = 0.018). τ is potentially an integrative marker of the changes occurring in cerebral vasculature, as it encompasses the interplay between changes in compliance and resistance that occur with age.

Sex differences in post-acute neurological sequelae of SARS-CoV-2 and symptom resolution in adults after coronavirus disease 2019 hospitalization: an international multi-centre prospective observational study.

Although it is known that coronavirus disease 2019 can present with a range of neurological manifestations and in-hospital complications, sparse data exist on whether these initial neurological symptoms of coronavirus disease 2019 are closely associated with post-acute neurological sequelae of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2; PANSC) and whether female versus male sex impacts symptom resolution. In this international, multi-centre, prospective, observational study across 407 sites from 15 countries (30 January 2020 to 30 April 2022), we report the prevalence and risk factors of PANSC among hospitalized adults and investigate the differences between males and females on neurological symptom resolution over time. PANSC symptoms included altered consciousness/confusion, fatigue/malaise, anosmia, dysgeusia and muscle ache/joint pain, on which information was collected at index hospitalization and during follow-up assessments. The analysis considered a time to the resolution of individual and all neurological symptoms. The resulting times were modelled by Weibull regression, assuming mixed-case interval censoring, with sex and age included as covariates. The model results were summarized as cumulative probability functions and age-adjusted and sex-adjusted median times to resolution. We included 6862 hospitalized adults with coronavirus disease 2019, who had follow-up assessments. The median age of the participants was 57 years (39.2% females). Males and females had similar baseline characteristics, except that more males (versus females) were admitted to the intensive care unit (30.5 versus 20.3%) and received mechanical ventilation (17.2 versus 11.8%). Approximately 70% of patients had multiple neurological symptoms at the first follow-up (median = 102 days). Fatigue (49.9%) and myalgia/arthralgia (45.2%) were the most prevalent symptoms of PANSC at the initial follow-up. The reported prevalence in females was generally higher (versus males) for all symptoms. At 12 months, anosmia and dysgeusia were resolved in most patients, although fatigue, altered consciousness and myalgia remained unresolved in >10% of the cohort. Females had a longer time to the resolution (5.2 versus 3.4 months) of neurological symptoms at follow-up for those with more than one neurological symptom. In the multivariable analysis, males were associated with a shorter time to the resolution of symptoms (hazard ratio = 1.53; 95% confidence interval = 1.39-1.69). Intensive care unit admission was associated with a longer time to the resolution of symptoms (hazard ratio = 0.68; 95% confidence interval = 0.60-0.77). Post-discharge stroke was uncommon (0.3% in females and 0.5% in males). Despite the methodological challenges involved in the collection of survey data, this international multi-centre prospective cohort study demonstrated that PANSC following index hospitalization was high. Symptom prevalence was higher and took longer to resolve in females than in males. This supported the fact that while males were sicker during acute illness, females were disproportionately affected by PANSC.

Lower (1,3)-beta-d-glucan sensitivity and in vitro levels in Candida auris and Candida parapsilosis strains.

OBJECTIVES: The serum (1,3)-beta-d-glucan (BDG) assay gives quicker results and has higher sensitivity than blood cultures, therefore it is advised for early diagnosis of invasive candidemia and/or discontinuation of empirical therapy. Its sensitivity may depend on different factors. The aim of our study was to analyse the in vitro and in vivo BDG levels in clinical isolates of three species of Candida responsible for candidemia. METHODS: C. albicans, C. parapsilosis, and C. auris strains were collected from blood cultures of patients who had a concurrent (-1 to +3 days) serum BDG test (Fungitell assay). Supernatants of all strains were tested in quadruplicate for BDG levels. RESULTS: Twenty-two C. auris, 14 C. albicans, and ten C. parapsilosis strains were included. The median BDG levels in supernatants were 463 pg/mL (interquartile range [IQR] 379-648) for C. auris, 1080 pg/mL (IQR 830-1276) for C. albicans, and 755 pg/mL (IQR 511-930) for C. parapsilosis, with the significant difference among the species (p < 0.0001). Median serum BDG levels (IQR) were significantly lower in case C. auris and C. parapsilosis vs. C. albicans (p < 0.0001), respectively, 50 pg/mL (IQR 15-161) and 57 pg/mL (IQR 18-332), vs. 372 pg/mL (IQR 102-520). Sensitivity of serum BDG was 39% (95% confidence interval [CI], 18-64) in case of C. auris, 30% (95% CI, 8-65) C. parapsilosis and 78% (95% CI, 49-94) C. albicans candidemia. DISCUSSION: In our centre C. auris and C. parapsilosis strains have lower BDG content as compared with C. albicans, with a potential impact on serum BDG performance for the diagnosis of candidemia.

Neuromonitoring in the ICU - what, how and why?

PURPOSE OF REVIEW: We selectively review emerging noninvasive neuromonitoring techniques and the evidence that supports their use in the ICU setting. The focus is on neuromonitoring research in patients with acute brain injury. RECENT FINDINGS: Noninvasive intracranial pressure evaluation with optic nerve sheath diameter measurements, transcranial Doppler waveform analysis, or skull mechanical extensometer waveform recordings have potential safety and resource-intensity advantages when compared to standard invasive monitors, however each of these techniques has limitations. Quantitative electroencephalography can be applied for detection of cerebral ischemia and states of covert consciousness. Near-infrared spectroscopy may be leveraged for cerebral oxygenation and autoregulation computation. Automated quantitative pupillometry and heart rate variability analysis have been shown to have diagnostic and/or prognostic significance in selected subtypes of acute brain injury. Finally, artificial intelligence is likely to transform interpretation and deployment of neuromonitoring paradigms individually and when integrated in multimodal paradigms. SUMMARY: The ability to detect brain dysfunction and injury in critically ill patients is being enriched thanks to remarkable advances in neuromonitoring data acquisition and analysis. Studies are needed to validate the accuracy and reliability of these new approaches, and their feasibility and implementation within existing intensive care workflows.

Non-invasive technology for brain monitoring: definition and meaning of the principal parameters for the International PRactice On TEChnology neuro-moniToring group (I-PROTECT).

Technologies for monitoring organ function are rapidly advancing, aiding physicians in the care of patients in both operating rooms (ORs) and intensive care units (ICUs). Some of these emerging, minimally or non-invasive technologies focus on monitoring brain function and ensuring the integrity of its physiology. Generally, the central nervous system is the least monitored system compared to others, such as the respiratory, cardiovascular, and renal systems, even though it is a primary target in most therapeutic strategies. Frequently, the effects of sedatives, hypnotics, and analgesics are entirely unpredictable, especially in critically ill patients with multiple organ failure. This unpredictability exposes them to the risks of inadequate or excessive sedation/hypnosis, potentially leading to complications and long-term negative outcomes. The International PRactice On TEChnology neuro-moniToring group (I-PROTECT), comprised of experts from various fields of clinical neuromonitoring, presents this document with the aim of reviewing and standardizing the primary non-invasive tools for brain monitoring in anesthesia and intensive care practices. The focus is particularly on standardizing the nomenclature of different parameters generated by these tools. The document addresses processed electroencephalography, continuous/quantitative electroencephalography, brain oxygenation through near-infrared spectroscopy, transcranial Doppler, and automated pupillometry. The clinical utility of the key parameters available in each of these tools is summarized and explained. This comprehensive review was conducted by a panel of experts who deliberated on the included topics until a consensus was reached. Images and tables are utilized to clarify and enhance the understanding of the clinical significance of non-invasive neuromonitoring devices within these medical settings.

Management of Neuromuscular Blocking Agents in Critically Ill Patients with Lung Diseases.

The use of neuromuscular blocking agents (NMBAs) is common in the intensive care unit (ICU). NMBAs have been used in critically ill patients with lung diseases to optimize mechanical ventilation, prevent spontaneous respiratory efforts, reduce the work of breathing and oxygen consumption, and avoid patient-ventilator asynchrony. In patients with acute respiratory distress syndrome (ARDS), NMBAs reduce the risk of barotrauma and improve oxygenation. Nevertheless, current guidelines and evidence are contrasting regarding the routine use of NMBAs. In status asthmaticus and acute exacerbation of chronic obstructive pulmonary disease, NMBAs are used in specific conditions to ameliorate patient-ventilator synchronism and oxygenation, although their routine use is controversial. Indeed, the use of NMBAs has decreased over the last decade due to potential adverse effects, such as immobilization, venous thrombosis, patient awareness during paralysis, development of critical illness myopathy, autonomic interactions, ICU-acquired weakness, and residual paralysis after cessation of NMBAs use. The aim of this review is to highlight current knowledge and synthesize the evidence for the effects of NMBAs for critically ill patients with lung diseases, focusing on patient-ventilator asynchrony, ARDS, status asthmaticus, and chronic obstructive pulmonary disease.

The Impact of Inotropes and Vasopressors on Cerebral Oxygenation in Patients with Traumatic Brain Injury and Subarachnoid Hemorrhage: A Narrative Review.

Traumatic brain injury (TBI) and subarachnoid hemorrhage (SAH) are critical neurological conditions that necessitate specialized care in the Intensive Care Unit (ICU). Managing cerebral perfusion pressure (CPP) and mean arterial pressure (MAP) is of primary importance in these patients. To maintain targeted MAP and CPP, vasopressors and/or inotropes are commonly used. However, their effects on cerebral oxygenation are not fully understood. The aim of this review is to provide an up-to date review regarding the current uses and pathophysiological issues related to the use of vasopressors and inotropes in TBI and SAH patients. According to our findings, despite achieving similar hemodynamic parameters and CPP, the effects of various vasopressors and inotropes on cerebral oxygenation, local CBF and metabolism are heterogeneous. Therefore, a more accurate understanding of the cerebral activity of these medications is crucial for optimizing patient management in the ICU setting.

Short-term mild hyperventilation on intracranial pressure, cerebral autoregulation, and oxygenation in acute brain injury patients: a prospective observational study.

Current guidelines suggest a target of partial pressure of carbon dioxide (PaCO2) of 32-35 mmHg (mild hypocapnia) as tier 2 for the management of intracranial hypertension. However, the effects of mild hyperventilation on cerebrovascular dynamics are not completely elucidated. The aim of this study is to evaluate the changes of intracranial pressure (ICP), cerebral autoregulation (measured through pressure reactivity index, PRx), and regional cerebral oxygenation (rSO2) parameters before and after induction of mild hyperventilation. Single center, observational study including patients with acute brain injury (ABI) admitted to the intensive care unit undergoing multimodal neuromonitoring and requiring titration of PaCO2 values to mild hypocapnia as tier 2 for the management of intracranial hypertension. Twenty-five patients were included in this study (40% female), median age 64.7 years (Interquartile Range, IQR = 45.9-73.2). Median Glasgow Coma Scale was 6 (IQR = 3-11). After mild hyperventilation, PaCO2 values decreased (from 42 (39-44) to 34 (32-34) mmHg, p < 0.0001), ICP and PRx significantly decreased (from 25.4 (24.1-26.4) to 17.5 (16-21.2) mmHg, p < 0.0001, and from 0.32 (0.1-0.52) to 0.12 (-0.03-0.23), p < 0.0001). rSO2 was statistically but not clinically significantly reduced (from 60% (56-64) to 59% (54-61), p < 0.0001), but the arterial component of rSO2 (ΔO2Hbi, changes in concentration of oxygenated hemoglobin of the total rSO2) decreased from 3.83 (3-6.2) µM.cm to 1.6 (0.5-3.1) µM.cm, p = 0.0001. Mild hyperventilation can reduce ICP and improve cerebral autoregulation, with minimal clinical effects on cerebral oxygenation. However, the arterial component of rSO2 was importantly reduced. Multimodal neuromonitoring is essential when titrating PaCO2 values for ICP management.

The Effect of Recruitment Maneuvers on Cerebrovascular Dynamics and Right Ventricular Function in Patients with Acute Brain Injury: A Single-Center Prospective Study.

BACKGROUND: Optimization of ventilatory settings is challenging for patients in the neurointensive care unit, requiring a balance between precise gas exchange control, lung protection, and managing hemodynamic effects of positive pressure ventilation. Although recruitment maneuvers (RMs) may enhance oxygenation, they could also exert profound undesirable systemic impacts. METHODS: The single-center, prospective study investigated the effects of RMs (up-titration of positive end-expiratory pressure) on multimodal neuromonitoring in patients with acute brain injury. Our primary focus was on intracranial pressure and secondarily on cerebral perfusion pressure (CPP) and other neurological parameters: cerebral autoregulation [pressure reactivity index (PRx)] and regional cerebral oxygenation (rSO2). We also assessed blood pressure and right ventricular (RV) function evaluated using tricuspid annular plane systolic excursion. Results are expressed as the difference (Δ) from baseline values obtained after completing the RMs. RESULTS: Thirty-two patients were enrolled in the study. RMs resulted in increased intracranial pressure (Δ = 4.8 mm Hg) and reduced CPP (ΔCPP = -12.8 mm Hg) and mean arterial pressure (difference in mean arterial pressure = -5.2 mm Hg) (all p < 0.001). Cerebral autoregulation worsened (ΔPRx = 0.31 a.u.; p < 0.001). Despite higher systemic oxygenation (difference in partial pressure of O2 = 4 mm Hg; p = 0.001) and unchanged carbon dioxide levels, rSO2 marginally decreased (ΔrSO2 = -0.5%; p = 0.031), with a significant drop in arterial content and increase in the venous content. RV systolic function decreased (difference in tricuspid annular plane systolic excursion = -0.1 cm; p < 0.001) with a tendency toward increased RV basal diameter (p = 0.06). Grouping patients according to ΔCPP or ΔPRx revealed that those with poorer tolerance to RMs had higher CPP (p = 0.040) and a larger RV basal diameter (p = 0.034) at baseline. CONCLUSIONS: In patients with acute brain injury, RMs appear to have adverse effects on cerebral hemodynamics. These findings might be partially explained by RM's impact on RV function. Further advanced echocardiography monitoring is required to prove this hypothesis.

The Role of Ultrasonography in the Process of Weaning from Mechanical Ventilation in Critically Ill Patients.

Weaning patients from mechanical ventilation (MV) is a complex process that may result in either success or failure. The use of ultrasound at the bedside to assess organs may help to identify the underlying mechanisms that could lead to weaning failure and enable proactive measures to minimize extubation failure. Moreover, ultrasound could be used to accurately identify pulmonary diseases, which may be responsive to respiratory physiotherapy, as well as monitor the effectiveness of physiotherapists' interventions. This article provides a comprehensive review of the role of ultrasonography during the weaning process in critically ill patients.