Lung-Protective Mechanical Ventilation in Patients with Severe Acute Brain Injury: A Multicenter Randomized Clinical Trial (PROLABI).

Rationale: Lung-protective strategies using low Vt and moderate positive end-expiratory pressure (PEEP) are considered best practice in critical care, but interventional trials have never been conducted in patients with acute brain injuries because of concerns about carbon dioxide control and the effect of PEEP on cerebral hemodynamics. Objectives: To test the hypothesis that ventilation with lower VT and higher PEEP compared to conventional ventilation would improve clinical outcomes in patients with acute brain injury. Methods: In this multicenter, open-label, controlled clinical trial, 190 adult patients with acute brain injury were assigned to receive either a lung-protective or a conventional ventilatory strategy. The primary outcome was a composite endpoint of death, ventilator dependency, and acute respiratory distress syndrome (ARDS) at Day 28. Neurological outcome was assessed at ICU discharge by the Oxford Handicap Scale and at 6 months by the Glasgow Outcome Scale. Measurements and Main Results: The two study arms had similar characteristics at baseline. In the lung-protective and conventional strategy groups, using an intention-to-treat approach, the composite outcome at 28 days was 61.5% and 45.3% (relative risk [RR], 1.35; 95% confidence interval [CI], 1.03-1.79; P = 0.025). Mortality was 28.9% and 15.1% (RR, 1.91; 95% CI, 1.06-3.42; P = 0.02), ventilator dependency was 42.3% and 27.9% (RR, 1.52; 95% CI, 1.01-2.28; P = 0.039), and incidence of ARDS was 30.8% and 22.1% (RR, 1.39; 95% CI, 0.85-2.27; P = 0.179), respectively. The trial was stopped after enrolling 190 subjects because of termination of funding. Conclusions: In patients with acute brain injury without ARDS, a lung-protective ventilatory strategy, as compared with a conventional strategy, did not reduce mortality, percentage of patients weaned from mechanical ventilation, or incidence of ARDS and was not beneficial in terms of neurological outcomes. Because of the early termination, these preliminary results require confirmation in larger trials. Clinical trial registered with www.clinicaltrials.gov (NCT01690819).

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.

Transcranial Doppler and Color-Coded Doppler Use for Brain Death Determination in Adult Patients: A Pictorial Essay.

Transcranial Doppler (TCD) is a repeatable, at-the-bedside, helpful tool for confirming cerebral circulatory arrest (CCA). Despite its variable accuracy, TCD is increasingly used during brain death determination, and it is considered among the optional ancillary tests in several countries. Among its limitations, the need for skilled operators with appropriate knowledge of typical CCA patterns and the lack of adequate acoustic bone windows for intracranial arteries assessment are critical. The purpose of this review is to describe how to evaluate cerebral circulatory arrest in the intensive care unit with TCD and transcranial duplex color-coded doppler (TCCD).

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.

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.

Electrocardiogram alterations in non-traumatic brain injury: a systematic review.

The presence of abnormal electrocardiograms in individuals without known organic heart disease is one of the most common manifestations of cardiac dysfunction occurring during acute non traumatic brain injury. The primary goal of the present review is to provide an overview of the available data and literature regarding the presence of new-onset electrocardiographic (ECG) alterations in acute non traumatic brain injury. The secondary aim is to identify the incidence of ECG alterations and consider the prognostic significance of new-onset ECG changes in this setting. To do so, English language articles from January 2000 to January 2022 were included from PubMed using the following keywords: "electrocardiogram and subarachnoid hemorrhage", "electrocardiogram and intracranial hemorrhage", "Q-T interval and subarachnoid hemorrhage ", "Q-T interval and intracranial bleeding ", "Q-T interval and intracranial hemorrhage", and "brain and heart- interaction in stroke". Of 3162 papers, 27 original trials looking at electrocardiogram alterations in acute brain injury were included following the PRISMA guideline. ECG abnormalities associated with acute brain injury could potentially predict poor patient outcomes. They could even herald the future development of neurogenic pulmonary edema (NPE), delayed cerebral ischemia (DCI), and even in-hospital death. In particular, patients with SAH are at increased risk of having severe ventricular dysrhythmias. These may contribute to a high mortality rate and to poor functional outcome at 3 months. The current data on ECG QT dispersion and mortality appear less clearly associated. While some patients demonstrated poor outcomes, others showed no relationship with poor outcomes or increased in-hospital mortality. Observing ECG alterations carefully after cerebral damage is important in the critical care of these patients as it can expose preexisting myocardial disease and change prognosis.

Illness Weakness, Polyneuropathy and Myopathy: Diagnosis, treatment, and long-term outcomes.

BACKGROUND: Severe weakness associated with critical illness (CIW) is common. This narrative review summarizes the latest scientific insights and proposes a guide for clinicians to optimize the diagnosis and management of the CIW during the various stages of the disease from the ICU to the community stage. MAIN BODY: CIW arises as diffuse, symmetrical weakness after ICU admission, which is an important differentiating factor from other diseases causing non-symmetrical muscle weakness or paralysis. In patients with adequate cognitive function, CIW can be easily diagnosed at the bedside using manual muscle testing, which should be routinely conducted until ICU discharge. In patients with delirium or coma or those with prolonged, severe weakness, specific neurophysiological investigations and, in selected cases, muscle biopsy are recommended. With these exams, CIW can be differentiated into critical illness polyneuropathy or myopathy, which often coexist. On the general ward, CIW is seen in patients with prolonged previous ICU treatment, or in those developing a new sepsis. Respiratory muscle weakness can cause neuromuscular respiratory failure, which needs prompt recognition and rapid treatment to avoid life-threatening situations. Active rehabilitation should be reassessed and tailored to the new patient's condition to reduce the risk of disease progression. CIW is associated with long-term physical, cognitive and mental impairments, which emphasizes the need for a multidisciplinary model of care. Follow-up clinics for patients surviving critical illness may serve this purpose by providing direct clinical support to patients, managing referrals to other specialists and general practitioners, and serving as a platform for research to describe the natural history of post-intensive care syndrome and to identify new therapeutic interventions. This surveillance should include an assessment of the activities of daily living, mood, and functional mobility. Finally, nutritional status should be longitudinally assessed in all ICU survivors and incorporated into a patient-centered nutritional approach guided by a dietician. CONCLUSIONS: Early ICU mobilization combined with the best evidence-based ICU practices can effectively reduce short-term weakness. Multi-professional collaborations are needed to guarantee a multi-dimensional evaluation and unitary community care programs for survivors of critical illnesses.

Targeted temperature management in patients with intracerebral haemorrhage, subarachnoid haemorrhage, or acute ischaemic stroke: updated consensus guideline recommendations by the Neuroprotective Therapy Consensus Review (NTCR) group.

BACKGROUND: There is a lack of consistent, evidence-based guidelines for the management of patients with fever after brain injury. The aim was to update previously published consensus recommendations on targeted temperature management after intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, and acute ischaemic stroke in patients who require admission to critical care. METHODS: A modified Delphi consensus, the Neuroprotective Therapy Consensus Review (NTCR), included 19 international neuro-intensive care experts with a subspecialty interest in the acute management of intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, and acute ischaemic stroke. An online, anonymised survey was completed ahead of the meeting before the group came together to consolidate consensus and finalise recommendations on targeted temperature management. A threshold of ≥80% for consensus was set for all statements. RESULTS: Recommendations were formulated based on existing evidence, literature review, and consensus. After intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, and acute ischaemic stroke in patients who require critical care admission, core temperature should ideally be monitored continuously and maintained between 36.0°C and 37.5°C using automated feedback-controlled devices, where possible. Targeted temperature management should be commenced within 1 h of first fever identification with appropriate diagnosis and treatment of infection, maintained for as long as the brain remains at risk of secondary injury, and rewarming should be controlled. Shivering should be monitored and managed to limit risk of secondary injury. Following a single protocol for targeted temperature management across intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, and acute ischaemic stroke is desirable. CONCLUSIONS: Based on a modified Delphi expert consensus process, these guidelines aim to improve the quality of targeted temperature management for patients after intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, and acute ischaemic stroke in critical care, highlighting the need for further research to improve clinical guidelines in this setting.

Evaluation and application of ultra-low-frequency pressure reactivity index in pediatric traumatic brain injury patients.

PURPOSE: While clinical practice suggests that knowing the cerebral autoregulation (CA) status of traumatic brain injury (TBI) patients is crucial in assessing the best treatment, evidence in pediatric TBI (pTBI) is limited. The pressure reactivity index (PRx) is a surrogate method for the continuous estimation of CA in adults; however, calculations require continuous, high-resolution monitoring data. We evaluate an ultra-low-frequency pressure reactivity index (UL-PRx), based on data sampled at ∼5-min periods, and test its association with 6-month mortality and unfavorable outcome in a cohort of pTBI patients. METHODS: Data derived from pTBI patients (0-18 years) requiring intracranial pressure (ICP) monitoring were retrospectively collected and processed in MATLAB using an in-house algorithm. RESULTS: Data on 47 pTBI patients were included. UL-PRx mean values, ICP, cerebral perfusion pressure (CPP), and derived indices showed significant association with 6-month mortality and unfavorable outcome. A value of UL-PRx of 0.30 was identified as the threshold to better discriminate both surviving vs deceased patients (AUC: 0.90), and favorable vs unfavorable outcomes (AUC: 0.70) at 6 months. At multivariate analysis, mean UL-PRx and % time with ICP > 20 mmHg, remained significantly associated with 6-month mortality and unfavorable outcome, even when adjusted for International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT)-Core variables. In six patients undergoing secondary decompressive craniectomy, no significant changes in UL-PRx were found after surgery. CONCLUSIONS: UL-PRx is associated with a 6-month outcome even if adjusted for IMPACT-Core. Its application in pediatric intensive care unit could be useful to evaluate CA and offer possible prognostic and therapeutic implications in pTBI patients. CLINICALTRIALS: GOV: NCT05043545, September 14, 2021, retrospectively registered.

Processed Electroencephalogram-Based Monitoring to Guide Sedation in Critically Ill Adult Patients: Recommendations from an International Expert Panel-Based Consensus.

BACKGROUND: The use of processed electroencephalography (pEEG) for depth of sedation (DOS) monitoring is increasing in anesthesia; however, how to use of this type of monitoring for critical care adult patients within the intensive care unit (ICU) remains unclear. METHODS: A multidisciplinary panel of international experts consisting of 21 clinicians involved in monitoring DOS in ICU patients was carefully selected on the basis of their expertise in neurocritical care and neuroanesthesiology. Panelists were assigned four domains (techniques for electroencephalography [EEG] monitoring, patient selection, use of the EEG monitors, competency, and training the principles of pEEG monitoring) from which a list of questions and statements was created to be addressed. A Delphi method based on iterative approach was used to produce the final statements. Statements were classified as highly appropriate or highly inappropriate (median rating ≥ 8), appropriate (median rating ≥ 7 but < 8), or uncertain (median rating < 7) and with a strong disagreement index (DI) (DI < 0.5) or weak DI (DI ≥ 0.5 but < 1) consensus. RESULTS: According to the statements evaluated by the panel, frontal pEEG (which includes a continuous colored density spectrogram) has been considered adequate to monitor the level of sedation (strong consensus), and it is recommended by the panel that all sedated patients (paralyzed or nonparalyzed) unfit for clinical evaluation would benefit from DOS monitoring (strong consensus) after a specific training program has been performed by the ICU staff. To cover the gap between knowledge/rational and routine application, some barriers must be broken, including lack of knowledge, validation for prolonged sedation, standardization between monitors based on different EEG analysis algorithms, and economic issues. CONCLUSIONS: Evidence on using DOS monitors in ICU is still scarce, and further research is required to better define the benefits of using pEEG. This consensus highlights that some critically ill patients may benefit from this type of neuromonitoring.

Physical, cognitive and mental health outcomes in 1-year survivors of COVID-19-associated ARDS.

We report on the outcome of 114 COVID-19-associated acute respiratory distress syndrome (ARDS) survivors evaluated at 3, 6 and 12 months after intensive care unit discharge with assessment of physical, mental and cognitive impairments. Critical illness polyneuromyopathy was diagnosed in 23 patients (39%). Handgrip dynamometry was 70% predicted at 3 months and significantly improved over time, whereas the 6 min walk test (80% predicted) and severe fatigue (27% of patients) did not. Independence in activities of daily living (ADL) was achieved by 98% at 3 months. Cognitive impairment (28% at 3 months) improved over time, whereas depression, anxiety and post-traumatic stress disorder symptoms, present in 9%, 10% and 4% at 3 months, did not. Normalised health-related quality of life was good. COVID-19-associated ARDS leads to persisting impairment in performance-based measures of physical function, while ADL, cognitive and mental health status, and health-related quality of life may be less impaired. Trial registration number NCT04608994.

Guillain-Barré syndrome and COVID-19: A 1-year observational multicenter study.

BACKGROUND AND PURPOSE: Many single cases and small series of Guillain-Barré syndrome (GBS) associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were reported during the coronavirus disease 19 (COVID-19) outbreak worldwide. However, the debate regarding the possible role of infection in causing GBS is still ongoing. This multicenter study aimed to evaluate epidemiological and clinical findings of GBS diagnosed during the COVID-19 pandemic in northeastern Italy in order to further investigate the possible association between GBS and COVID-19. METHODS: Guillain-Barré syndrome cases diagnosed in 14 referral hospitals from northern Italy between March 2020 and March 2021 were collected and divided into COVID-19-positive and COVID-19-negative. As a control population, GBS patients diagnosed in the same hospitals from January 2019 to February 2020 were considered. RESULTS: The estimated incidence of GBS in 2020 was 1.41 cases per 100,000 persons/year (95% confidence interval 1.18-1.68) versus 0.89 cases per 100,000 persons/year (95% confidence interval 0.71-1.11) in 2019. The cumulative incidence of GBS increased by 59% in the period March 2020-March 2021 and, most importantly, COVID-19-positive GBS patients represented about 50% of the total GBS cases with most of them occurring during the two first pandemic waves in spring and autumn 2020. COVID-19-negative GBS cases from March 2020 to March 2021 declined by 22% compared to February 2019-February 2020. CONCLUSIONS: Other than showing an increase of GBS in northern Italy in the "COVID-19 era" compared to the previous year, this study emphasizes how GBS cases related to COVID-19 represent a significant part of the total, thus suggesting a relation between COVID-19 and GBS.

Transcranial Doppler as a screening test to exclude intracranial hypertension in brain-injured patients: the IMPRESSIT-2 prospective multicenter international study.

BACKGROUND: Alternative noninvasive methods capable of excluding intracranial hypertension through use of transcranial Doppler (ICPtcd) in situations where invasive methods cannot be used or are not available would be useful during the management of acutely brain-injured patients. The objective of this study was to determine whether ICPtcd can be considered a reliable screening test compared to the reference standard method, invasive ICP monitoring (ICPi), in excluding the presence of intracranial hypertension. METHODS: This was a prospective, international, multicenter, unblinded, diagnostic accuracy study comparing the index test (ICPtcd) with a reference standard (ICPi), defined as the best available method for establishing the presence or absence of the condition of interest (i.e., intracranial hypertension). Acute brain-injured patients pertaining to one of four categories: traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), intracerebral hemorrhage (ICH) or ischemic stroke (IS) requiring ICPi monitoring, were enrolled in 16 international intensive care units. ICPi measurements (reference test) were compared to simultaneous ICPtcd measurements (index test) at three different timepoints: before, immediately after and 2 to 3 h following ICPi catheter insertion. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) were calculated at three different ICPi thresholds (> 20, > 22 and > 25 mmHg) to assess ICPtcd as a bedside real-practice screening method. A receiver operating characteristic (ROC) curve analysis with the area under the curve (AUC) was used to evaluate the discriminative accuracy and predictive capability of ICPtcd. RESULTS: Two hundred and sixty-two patients were recruited for final analysis. Intracranial hypertension (> 22 mmHg) occurred in 87 patients (33.2%). The total number of paired comparisons between ICPtcd and ICPi was 687. The NPV was elevated (ICP > 20 mmHg = 91.3%, > 22 mmHg = 95.6%, > 25 mmHg = 98.6%), indicating high discriminant accuracy of ICPtcd in excluding intracranial hypertension. Concordance correlation between ICPtcd and ICPi was 33.3% (95% CI 25.6-40.5%), and Bland-Altman showed a mean bias of -3.3 mmHg. The optimal ICPtcd threshold for ruling out intracranial hypertension was 20.5 mmHg, corresponding to a sensitivity of 70% (95% CI 40.7-92.6%) and a specificity of 72% (95% CI 51.9-94.0%) with an AUC of 76% (95% CI 65.6-85.5%). CONCLUSIONS AND RELEVANCE: ICPtcd has a high NPV in ruling out intracranial hypertension and may be useful to clinicians in situations where invasive methods cannot be used or not available. TRIAL REGISTRATION: NCT02322970 .

Aneurismal subarachnoid hemorrhage during the COVID-19 outbreak in a Hub and Spoke system: observational multicenter cohort study in Lombardy, Italy.

BACKGROUND: Lombardy was the most affected Italian region by the first phase of the COVID-19 pandemic and underwent urgent reorganization for the management of emergencies, including subarachnoid hemorrhage from a ruptured cerebral aneurysm (aSAH). The aim of the study was to define demographics, clinical, and therapeutic features of aSAH during the COVID-19 outbreak and compare these with a historical cohort. METHODS: In this observational multicenter cohort study, patients aged 18 years or older, who were diagnosed with aSAH at the participating centers in Lombardy from March 9 to May 10, 2020, were included (COVID-19 group). In order to minimize bias related to possible SAH seasonality, the control group was composed of patients diagnosed with aSAH from March 9 to May 10 of the three previous years, 2017-2018-2019 (pre-pandemic group). Twenty-three demographic, clinical, and therapeutic features were collected. Statistical analysis was performed. RESULTS: Seventy-two patients during the COVID-19 period and 179 in the control group were enrolled at 14 centers. Only 4 patients were positive for SARS-CoV-2. The "diagnostic delay" was significantly increased (+ 68%) in the COVID-19 group vs. pre-pandemic (1.06 vs. 0.63 days, respectively, p-value = 0.030), while "therapeutic delay" did not differ significantly between the two periods (0.89 vs. 0.74 days, p-value = 0.183). Patients with poor outcome (GOS at discharge from 1 to 3) were higher during the COVID-19 period (54.2%) compared to pre-pandemic (40.2%, p = 0.044). In logistic regression analysis, in which outcome was the dichotomized Glasgow Outcome Scale (GOS), five variables showed p-values < 0.05: age at admission, WFNS grade, treatment (none), days in ICU, and ischemia. CONCLUSIONS: We documented a significantly increased "diagnostic delay" for subarachnoid hemorrhages during the first COVID-19 outbreak in Lombardy. However, despite the dramatic situation that the healthcare system was experiencing, the Lombardy regional reorganization model, which allowed centralization of neurosurgical emergencies such as SAHs, avoided a "therapeutic delay" and led to results overall comparable to the control period.

Guillain-Barré syndrome and COVID-19: an observational multicentre study from two Italian hotspot regions.

OBJECTIVE: Single cases and small series of Guillain-Barré syndrome (GBS) have been reported during the SARS-CoV-2 outbreak worldwide. We evaluated incidence and clinical features of GBS in a cohort of patients from two regions of northern Italy with the highest number of patients with COVID-19. METHODS: GBS cases diagnosed in 12 referral hospitals from Lombardy and Veneto in March and April 2020 were retrospectively collected. As a control population, GBS diagnosed in March and April 2019 in the same hospitals were considered. RESULTS: Incidence of GBS in March and April 2020 was 0.202/100 000/month (estimated rate 2.43/100 000/year) vs 0.077/100 000/month (estimated rate 0.93/100 000/year) in the same months of 2019 with a 2.6-fold increase. Estimated incidence of GBS in COVID-19-positive patients was 47.9/100 000 and in the COVID-19-positive hospitalised patients was 236/100 000. COVID-19-positive patients with GBS, when compared with COVID-19-negative subjects, showed lower MRC sum score (26.3±18.3 vs 41.4±14.8, p=0.006), higher frequency of demyelinating subtype (76.6% vs 35.3%, p=0.011), more frequent low blood pressure (50% vs 11.8%, p=0.017) and higher rate of admission to intensive care unit (66.6% vs 17.6%, p=0.002). CONCLUSIONS: This study shows an increased incidence of GBS during the COVID-19 outbreak in northern Italy, supporting a pathogenic link. COVID-19-associated GBS is predominantly demyelinating and seems to be more severe than non-COVID-19 GBS, although it is likely that in some patients the systemic impairment due to COVID-19 might have contributed to the severity of the whole clinical picture.

Brain Injury in Extracorporeal Membrane Oxygenation: A Multidisciplinary Approach.

Extracorporeal membrane oxygenation (ECMO) represents an established technique to provide temporary cardiac and/or pulmonary support. ECMO, in veno-venous, veno-arterial or in extracorporeal carbon dioxide removal modality, is associated with a high rate of brain injuries. These complications have been reported in 7 to 15% of adults and 20% of neonates, and are associated with poor survival. Thromboembolic events, loss of cerebral autoregulation, alteration of the blood-brain barrier, and hemorrhage related to anticoagulation represent the main causes of severe brain injury during ECMO. The most frequent forms of acute neurological injuries in ECMO patients are intracranial hemorrhage (2-21%), ischemic stroke (2-10%), seizures (2-6%), and hypoxic-ischemic brain injury; brain death may also occur in this population. Other frequent complications are infarction (1-8%) and cerebral edema (2-10%), as well as neuropsychological and psychiatric sequelae, including posttraumatic stress disorder.

Essential Noninvasive Multimodality Neuromonitoring for the Critically Ill Patient.

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2020. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2020. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901.

Determination of Imminent Brain Death Using the Full Outline of Unresponsiveness Score and the Glasgow Coma Scale: A Prospective, Multicenter, Pilot Feasibility Study.

PURPOSE: To evaluate the accuracy of the imminent brain death (IBD) diagnosis in predicting brain death (BD) by daily assessment of the Full Outline of Unresponsiveness (FOUR) score and the Glasgow Coma Scale (GCS) with the assessment of brain stem reflexes. MATERIALS AND METHODS: Prospective multicenter pilot study carried out in 5 adult Italian intensive care units (ICUs). Imminent brain death was established when the FOUR score was 0 (IBD-FOUR) or the GCS score was 3 and at least 3 among pupillary light, corneal, pharyngeal, carinal, oculovestibular, and trigeminal reflexes were absent (IBD-GCS). RESULTS: A total of 219 neurologic evaluations were performed in 40 patients with deep coma at ICU admission (median GCS 3). Twenty-six had a diagnosis of IBD-FOUR, 27 of IBD-GCS, 14 were declared BD, and 9 were organ donors. The mean interval between IBD diagnosis and BD was 1.7 days (standard deviation [SD] 2.0 days) using IBD-FOUR and 2.0 days (SD 1.96 days) using IBD-GCS. Both FOUR and GCS had 100% sensitivity and low specificity (FOUR: 53.8%; GCS: 50.0%) in predicting BD. CONCLUSIONS: Daily IBD evaluation in the ICU is feasible using FOUR and GCS with the assessment of brain stem reflexes. Both scales had 100% sensitivity in predicting IBD, but FOUR may be preferable since it incorporates the pupillary, corneal, and cough reflexes and spontaneous breathing that are easily assessed in the ICU.

The IN-PANCIA Study: Clinical Evaluation of Gastrointestinal Dysfunction and Failure, Multiple Organ Failure, and Levels of Citrulline in Critically Ill Patients.

PURPOSE: Gastrointestinal dysfunction and failure (GID and GIF) in critically ill patients are a common, relevant, and underestimated complications in ICU patients. The aims of this study were (1) to determine plasmatic levels of citrulline, glutamine, and arginine as markers of GID/GIF in critically ill patients with or without GID/GIF with or without multiple organ failure (MOF) and (2) to assess the role of intra-abdominal hypertension in these patient groups. MATERIALS AND METHODS: This is a 1-year, monocentric (Italian hospital), prospective observational study. Inclusion criteria were adult patients with GID/GIF, with or without MOF. The GIF score was daily evaluated in 39 critically ill patients. Amino acids were measured at the time of GID or GIF. RESULTS: We enrolled 39 patients. Nine patients developed GID and 7 GIF; 6 of patients with GID/GIF developed MOF. Citrulline was lower (P < .001) in patients with GID/GIF (11.3 [4.4] µmol/L), compared to patients without GID/GIF (22.4 [6.8] µmol/L); likewise, glutamine was lower in patients with GID/GIF, whereas arginine was nonstatistically different between the 2 groups. Intra-abdominal pressure was higher in patients affected by MOF (13.0 [2.2] mm Hg) than in patients with GIF/GID without MOF (9.6 [2.6] mm Hg) and compared to patients without GID/GIF (7.2 [2.1] mm Hg). CONCLUSIONS: Both GID and GIF in critically ill patients are associated with low levels of citrulline and glutamine, which could be considered as markers of small bowel dysfunction. The higher the GIF score, the lower the citrulline levels. Patients affected by MOF had higher levels of intra-abdominal pressure.

Ultrasound non-invasive intracranial pressure assessment in paediatric neurocritical care: a pilot study.

BACKGROUND: The assessment of intracranial pressure (ICP) is essential in the management of neurocritical care paediatric patients. The gold standard for invasive ICP is an intraventricular catheter or intraparenchymal microsensor but is invasive and carries some risks. Therefore, a non-invasive method for measuring ICP (nICP) would be desirable especially in the paediatric population. The aim of this study is to assess the relationship between ICP and different ultrasound-based methods in neurocritical care paediatric patients. METHODS: Children aged < 16 years with indication for invasive ICP monitoring were prospectively enrolled. The following non-invasive methods were compared with the invasive gold standard: optic nerve sheath diameter ultrasound (ONSD)-derived nICP (nICPONSD); arterial TCD-derived pulsatility index (PIa) and a method based on the diastolic component of the TCD cerebral blood flow velocity and mean arterial blood pressure (nICPFVd). RESULTS: We analysed 107 measurements from 10 paediatric patients. Results from linear regression demonstrated that, among the nICP methods, ONSD has the best correlation with ICP (r = 0.852 (p < 0.0001)). Results from receiving operator curve analysis demonstrated that using a threshold of 15 mmHg, ONSD has and area under the curve (AUC) of 0.94 (95% CI = 0.892-0.989), with best threshold at 3.85 mm (sensitivity = 0.811; specificity = 0.939). CONCLUSIONS: Our preliminary results suggested that ONSD ultrasonography presents the best accuracy to assess ICP among the methods studied. Given its non-invasiveness, repeatability and safety, this technique has the potential of representing a valid option as non-invasive tool to assess the risk of intracranial hypertension in the paediatric population.