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).

Cerebro-spinal fluid glucose and lactate concentrations changes in response to therapies in patIents with primary brain injury: the START-TRIP study.

INTRODUCTION: Altered levels of cerebrospinal fluid (CSF) glucose and lactate concentrations are associated with poor outcomes in acute brain injury patients. However, no data on changes in such metabolites consequently to therapeutic interventions are available. The aim of the study was to assess CSF glucose-to-lactate ratio (CGLR) changes related to therapies aimed at reducing intracranial pressure (ICP). METHODS: A multicentric prospective cohort study was conducted in 12 intensive care units (ICUs) from September 2017 to March 2022. Adult (> 18 years) patients admitted after an acute brain injury were included if an external ventricular drain (EVD) for intracranial pressure (ICP) monitoring was inserted within 24 h of admission. During the first 48-72 h from admission, CGLR was measured before and 2 h after any intervention aiming to reduce ICP ("intervention"). Patients with normal ICP were also sampled at the same time points and served as the "control" group. RESULTS: A total of 219 patients were included. In the intervention group (n = 115, 53%), ICP significantly decreased and CPP increased. After 2 h from the intervention, CGLR rose in both the intervention and control groups, although the magnitude was higher in the intervention than in the control group (20.2% vs 1.6%; p = 0.001). In a linear regression model adjusted for several confounders, therapies to manage ICP were independently associated with changes in CGLR. There was a weak inverse correlation between changes in ICP and CGRL in the intervention group. CONCLUSIONS: In this study, CGLR significantly changed over time, regardless of the study group. However, these effects were more significant in those patients receiving interventions to reduce ICP.

Acute Headache Management for Patients with Subarachnoid Hemorrhage: An International Survey of Health Care Providers.

BACKGROUND: Severe headaches are common after subarachnoid hemorrhage. Guidelines recommend treatment with acetaminophen and opioids, but patient data show that headaches often persist despite multimodal treatment approaches. Considering an overall slim body of data for a common complaint affecting patients with SAH during their intensive care stay, we set out to assess practice patterns in headache management among clinicians who treat patients with SAH. METHODS: We conducted an international cross-sectional study through a 37-question Web-based survey distributed to members of five professional societies relevant to intensive and neurocritical care from November 2021 to January 2022. Responses were characterized through descriptive analyses. Fisher's exact test was used to test associations. RESULTS: Of 516 respondents, 329 of 497 (66%) were from North America and 121 of 497 (24%) from Europe. Of 435 respondents, 379 (87%) reported headache as a major management concern for patients with SAH. Intensive care teams were primarily responsible for analgesia during hospitalization (249 of 435, 57%), whereas responsibility shifted to neurosurgery at discharge (233 of 501, 47%). Most used medications were acetaminophen (90%), opioids (66%), corticosteroids (28%), and antiseizure medications (28%). Opioids or medication combinations including opioids were most frequently perceived as most effective by 169 of 433 respondents (39%, predominantly intensivists), followed by corticosteroids or combinations with corticosteroids (96 of 433, 22%, predominantly neurologists). Of medications prescribed at discharge, acetaminophen was most common (303 of 381, 80%), followed by opioids (175 of 381, 46%) and antiseizure medications (173 of 381, 45%). Opioids during hospitalization were significantly more prescribed by intensivists, by providers managing higher numbers of patients with SAH, and in Europe. At discharge, opioids were more frequently prescribed in North America. Of 435 respondents, 299 (69%) indicated no change in prescription practice of opioids with the opioid crisis. Additional differences in prescription patterns between continents and providers and while inpatient versus at discharge were found. CONCLUSIONS: Post-SAH headache in the intensive care setting is a major clinical concern. Analgesia heavily relies on opioids both in use and in perception of efficacy, with no reported change in prescription patterns for opioids for most providers despite the significant drawbacks of opioids. Responsibility for analgesia shifts between hospitalization and discharge. International and provider-related differences are evident. Novel treatment strategies and alignment of prescription between providers are urgently needed.

Neurogenic Fever after Subarachnoid Hemorrhage in Animal Models: A Systematic Review.

The observation of neurogenic fever resulting from subarachnoid hemorrhage (SAH) in animal models is a useful tool for the interpretation of its pathophysiology in humans, which is still a major challenge in the management of neurocritical patients. This systematic review aims to identify the prognostic factors and pathophysiological elements that determine the onset of neurogenic fever and its severity in animal models. In addition, our study aims to analyze which pharmacological treatments are most effective. All the articles available in Pubmed, Embase, and the Biological Science Collection until August 2021 concerning in vivo experimental studies on SAH animal models, including full texts and abstracts written in English and Italian, were considered. The risk of bias was assessed with SYRCLE's Risk of Bias tool. In total, 81 records were retrieved; after excluding duplicates, 76 records were potentially relevant. A total of 64 articles was excluded after title and abstract screening. The remaining 12 studies were evaluated as full texts, and 6 other studies were excluded (SAH-induced animal studies without a body temperature assessment). In one study, body temperature was measured after SAH induction, but the authors did not report temperature recording. Therefore, only five studies met the search criteria. The high methodological heterogeneity (different animal species, different temperature measurement methods, and different methods of the induction of bleeding) prevented meta-analysis. Synthesis methodology without meta-analysis (SWiM) was used for data analysis. The total number of animals used as controls was 87 (23 rabbits, 32 mice, and 32 rats), while there were 130 animals used as interventions (54 rabbits, 44 mice, and 32 rats). The presence of blood in the subarachnoid space, particularly red blood cells, is responsible for neurogenic fever; the role of hemoglobin is unclear. The mechanism is apparently not mediated by prostaglandins. The autonomic nervous system innervating brown adipose tissue is undoubtedly implicated in the onset of neurogenic fever. The activation of the central adenosine-1 receptor is effective in controlling the temperature of animals with neurogenic fever (by inhibiting thermogenesis of brown adipose tissue).

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 .

Yellow flag on prognostic factors for non-specific chronic low back pain patients subjected to mini-invasive treatment: a cohort study.

OBJECTIVES: Research was conducted to study the efficacy of analgesic infiltration treatment in a well-selected population of patients with non-specific drug-resistant chronic low back pain. It studied the pain on a numeric rating scale and the physical and mental condition of patients using a short-form health survey-36, before and six months after invasive pain treatment. DESIGN: This is a prospective observational single center cohort study. SETTING: The study took place in the Multimodal Pain Therapy Unit of the IRCCS Institute of Neurological Sciences in Bologna, Italy. SUBJECTS: Four hundred and thirteen out of a total 538 patients admitted to the unit with non-specific drug-resistant chronic low back pain were enrolled in the study. METHOD: Patients were enrolled with written consent between April 2017 and November 2018. The study assessed NRS, BDI and SF-36 scores before and six months after mini-invasive treatment. RESULTS: There is an inverse correlation between Mental Component Scale (MCS) and Physical component scale as measured by SF-36. Older patients in a worse physical condition but with a more positive outlook on their quality of life were more likely to improve after invasive treatment (p < 0.001). The BDI scale is more effective in the diagnosis of depression than MCS. CONCLUSIONS: The prognostic value of MCS given to the patient before mini-invasive treatment could lead physicians to adopt a multimodal approach that includes consideration of the psychological features of pain and possibly antidepressant therapy.

A Proposal for a New Protocol for Sonographic Assessment of the Optic Nerve Sheath Diameter: The CLOSED Protocol.

Measuring and monitoring of intracranial pressure is considered standard of care in patients with suspected intracranial hypertension. Sonographic assessment of the optic nerve sheath diameter (ONSD) has been promising and potentially useful for noninvasive intracranial hypertension screening. ONSD measurements are easy to perform, repeatable at bedside, fast, low cost, and radiation-free. However, they are still burdened by inter-rater variability, lack of ultrasound (US) setting standardization (e.g., US frequency, focus depth, etc.), and possible artifacts. To overcome this problem, we propose the CLOSED protocol associated with equipment specifications, as a guide to minimize the occurrence of such artifacts enabling a more reliable and accurate measurement. We suggest that color Doppler could be used as a new standard evaluation for the ONSD.

Unifying Children's Surgery and Anesthesia Stakeholders Across Institutions and Clinical Disciplines: Challenges and Solutions from Uganda.

BACKGROUND: There is a significant unmet need for children's surgical care in low- and middle-income countries (LMICs). Multidisciplinary collaboration is required to advance the surgical and anesthesia care of children's surgical conditions such as congenital conditions, cancer and injuries. Nonetheless, there are limited examples of this process from LMICs. We describe the development and 3-year outcomes following a 2015 stakeholders' meeting in Uganda to catalyze multidisciplinary and multi-institutional collaboration. METHODS: The stakeholders' meeting was a daylong conference held in Kampala with local, regional and international collaborators in attendance. Multiple clinical specialties including surgical subspecialists, pediatric anesthesia, perioperative nursing, pediatric oncology and neonatology were represented. Key thematic areas including infrastructure, training and workforce retention, service delivery, and research and advocacy were addressed, and short-term objectives were agreed upon. We reported the 3-year outcomes following the meeting by thematic area. RESULTS: The Pediatric Surgical Foundation was developed following the meeting to formalize coordination between institutions. Through international collaborations, operating room capacity has increased. A pediatric general surgery fellowship has expanded at Mulago and Mbarara hospitals supplemented by an international fellowship in multiple disciplines. Coordinated outreach camps have continued to assist with training and service delivery in rural regional hospitals. CONCLUSION: Collaborations between disciplines, both within LMICs and with international partners, are required to advance children's surgery. The unification of stakeholders across clinical disciplines and institutional partnerships can facilitate increased children's surgical capacity. Such a process may prove useful in other LMICs with a wide range of children's surgery stakeholders.

Giuseppe Dagnini (1866-1928): Discoverer of the Trigemino-Cardiac Reflex and Practical Implications in Neurosurgery and Other Medical Specialties.

The authors present the life and art of Giuseppe Dagnini, a renowned Italian physician who was born in Bologna in 1866. He was the chief of the Maggiore Hospital in Bologna and authored valuable scientific works on the trigemino-cardiac reflex which is still applied in modern clinical practice. Dr. Dagnini firstly described the reflex in 1908 postulating that stimulation of one of the 3 branches of the trigeminal nerve triggers the afferent pathway in lowering heart rate. The authors also provide a modern outlook on the clinical implications of the TCR in neurosurgery, neuroanesthesia, and other medical specialties.

Factors affecting 30-day mortality in poor-grade aneurysmal subarachnoid hemorrhage: a 10-year single-center experience.

Background: The management of patients with poor-grade aneurysmal subarachnoid hemorrhage (aSAH) is burdened by an unfavorable prognosis even with aggressive treatment. The aim of the present study is to investigate the risk factors affecting 30-day mortality in poor-grade aSAH patients. Methods: We performed a retrospective analysis of a prospectively collected database of poor-grade aSAH patients (World Federation of Neurosurgical Societies, WFNS, grades IV and V) treated at our institution from December 2010 to December 2020. For all variables, percentages of frequency distributions were analyzed. Contingency tables (Chi-squared test) were used to assess the association between categorical variables and outcomes in the univariable analysis. Multivariable analysis was performed by using the multiple logistic regression method to estimate the odds ratio (OR) for 30-day mortality. Results: A total of 149 patients were included of which 32% had WFNS grade 4 and 68% had WFNS grade 5. The overall 1-month mortality rate was 21%. On univariable analysis, five variables were found to be associated with the likelihood of death, including intraventricular hemorrhage (IVH ≥ 50 mL, p = 0.005), the total amount of intraventricular and intraparenchymal hemorrhage (IVH + ICH ≥ 90 mL, p = 0.019), the IVH Ratio (IVH Ratio ≥ 40%, p = 0.003), posterior circulation aneurysms (p = 0.019), presence of spot sign on initial CT scan angiography (p = 0.015).Nonetheless, when the multivariable analysis was performed, only IVH Ratio (p = 0.005; OR 3.97), posterior circulation aneurysms (p = 0.008; OR 4.05) and spot sign (p = 0.022; OR 6.87) turned out to be independent predictors of 30-day mortality. Conclusion: The risk of mortality in poor-grade aSAH remains considerable despite maximal treatment. Notwithstanding the limitations of a retrospective study, our report highlights some neuroradiological features that in the emergency setting, combined with leading clinical and anamnestic parameters, may support the multidisciplinary team in the difficult decision-making process and communication with family members from the earliest stages of poor-grade aSAH. Further prospective studies are warranted.

Hemorrhage Volume Drives Early Brain Injury and Outcome in Poor-Grade Aneurysmal SAH.

BACKGROUND AND PURPOSE: Early brain injury is a major determinant of clinical outcome in poor-grade (World Federation of Neurosurgical Societies [WFNS] IV-V) aneurysmal SAH and is radiologically defined by global cerebral edema. Little is known, though, about the effect of global intracranial hemorrhage volume on early brain injury development and clinical outcome. MATERIALS AND METHODS: Data from the multicentric prospective Poor-Grade Aneurysmal Subarachnoid Hemorrhage (POGASH) Registry of consecutive patients with poor-grade aneurysmal SAH admitted from January 1, 2015, to August 31, 2022, was retrospectively evaluated. Poor grade was defined according to the worst-pretreatment WFNS grade. Global intracranial hemorrhage volume as well as the volumes of intracerebral hemorrhage, intraventricular hemorrhage, and SAH were calculated by means of analytic software in a semiautomated setting. Outcomes included severe global cerebral edema (defined by Subarachnoid Hemorrhage Early Brain Edema Score grades 3-4), in-hospital mortality (mRS 6), and functional independence (mRS 0-2) at follow-up. RESULTS: Among 400 patients (median global intracranial hemorrhage volume of 91 mL; interquartile range, 59-128), severe global cerebral edema was detected in 218/400 (54.5%) patients. One hundred twenty-three (30.8%) patients died during the acute phase of hospitalization. One hundred fifty-five (38.8%) patients achieved mRS 0-2 at a median of 13 (interquartile range, 3-26) months of follow-up. Multivariable analyses showed global intracranial hemorrhage volume as independently associated with severe global cerebral edema (adjusted OR, 1.009; 95% CI, 1.004-1.014; P < .001), mortality (adjusted OR, 1.006; 95% CI, 1.001-1.01; P = .018) and worse clinical outcome (adjusted OR, 0.992; 95% CI, 0.98-0.996; P < .010). The effect of global intracranial hemorrhage volume on clinical-radiologic outcomes changed significantly according to different age groups (younger than 50, 50-70, older than 70 year of age). Volumes of intracerebral hemorrhage, intraventricular hemorrhage, and SAH affected the 3 predefined outcomes differently. Intracerebral hemorrhage volume independently predicted global cerebral edema and long-term outcome, intraventricular hemorrhage volume predicted mortality and long-term outcome, and SAH volume predicted long-term clinical outcome. CONCLUSIONS: Global intracranial hemorrhage volume plays a pivotal role in global cerebral edema development and emerged as an independent predictor of both mortality and long-term clinical outcome. Aging emerged as a reducing predictor in the relationship between global intracranial hemorrhage volume and global cerebral edema.

Magnetic Resonance-Based Assessment of Optic Nerve Sheath Diameter: A Prospective Observational Cohort Study on Inter- and Intra-Rater Agreement.

BACKGROUND: The measurement of optic nerve sheath diameter (ONSD) as a non-invasive method of estimating intracranial pressure has been widely reported in the literature. However, few studies have evaluated the accuracy of magnetic resonance imaging (MRI) in assessing ONSD measurements, although it is considered a very reliable method, it is not easily repeatable, expensive and is not readily available bedside. Herein, an assessment of the intra- and inter-rater reliability of ONSD assessment using MRI was conducted. METHODS: A consecutive, prospective cohort of patients with suspected idiopathic normal-pressure hydrocephalus was analyzed. ONSD MRI measurements of the transverse and sagittal diameters at a distance of 3 mm behind the papilla were evaluated twice each by two expert neuroradiologists. The correlations between MRI examiners were calculated using the concordance correlation coefficient (CCC). RESULTS: Fifty patients were included in the study. ONSD MRI average measurements were substantially higher than clinically expected (>5 mm). Considering intra-rater concordance, only one of the two neuroradiologists achieved an excellent score at CCC. Only a moderate inter-observer CCC for MRI assessment was found at all diameters. CONCLUSIONS: The use of a widespread MRI sequence (3D T1) to measure ONSD is not an accurate method since it may overestimate measurements and is dependent upon an operator.

Treatment of cerebral ventriculitis with a new self-irrigating catheter system: narrative review and case series.

Cerebral ventriculitis is a life-threatening condition that requires prompt and effective pharmacological intervention. The continuous irrigation of the cerebral ventricles with fluid and its drainage is a system to remove toxic substances and infectious residues in the ventricles; this system is called IRRAflow®. We used this kind of ventricular irrigation/drainage system to treat two patients with post-surgical cerebral ventriculitis and a patient with bacterial meningitis complicated with ventriculitis. In this case series, we discuss the management of these three cases of cerebral ventriculitis: we monitored cytochemical parameters and cultures of the cerebrospinal fluid of patients during their ICU stay and we observed a marked improvement after irrigation and drainage with IRRAflow® system. Irrigation/drainage catheter stay, mode settings, and antibiotic therapies were different among these three patients, and neurological outcomes were variable, according to their underlying pathologies. IRRAflow® system can be applied also in other types of brain injury, such as intraventricular hemorrhage, intracranial abscess, subdural hematomas, and intracerebral hemorrhage, with the aim to remove the hematic residues and enhance the functional recovery of the patients. IRRAflow® seems a promising and useful tool to treat infectious and hemorrhagic diseases in neuro-intensive care unit.

Management and outcomes of calf deep vein thrombosis in patients with contraindication to full anticoagulation due to bleeding.

BACKGROUND: This prospective observational study was aimed at assessing early outcomes of inpatients with isolated distal deep vein thrombosis (IDDVT) and coexisting bleeding. METHODS: Patients received enoxaparin 4000 units daily or intermediate doses, and ultrasound surveillance (US). Primary outcomes were extension to the popliteal vein (PDVT) or symptomatic pulmonary embolism (PE), bleeding complications during the treatment and the composite of PDVT and bleeding complications. Secondary outcomes were recurrent IDDVTs and death. RESULTS: 90/95 patients completed the study period (30 days). PDVT occurred in 2/41 (4.9%) and in 3/45 (6.7%) subjects receiving enoxaparin 4000 units and intermediate doses respectively (OR 1.39; 95% CI: 0.22-11; P=0.72). PE occurred in only one of the 4 untreated subjects (25% vs. 0 patients taking enoxaparin 4000 units or intermediate doses; P=1.0). Recurrent IDDVTs occurred in 29 subjects (32.2%), more frequently during enoxaparin 4000 (19/29, 65.5%). Four patients died (4.4%). Bleeding complications occurred in 8 subjects (8.9%), all treated with intermediate doses (0 vs. 17.8%; P=1.0). Enoxaparin 4000 units significantly reduced the risk of the composite outcome compared with higher doses (4.9% vs. 24.4%; OR 6.31; 95% CI: 1.56-42.65; P=0.02). Major trauma significantly increased the risk of PDVT (OR 20.92; 95% CI: 2.82-427.51, P=0.01; logistic regression P=0.01). Patients with major trauma are also at increased bleeding risk (OR 5; 95% CI: 1.06-23.76, P=0.04; logistic regression P=0.03). CONCLUSIONS: Enoxaparin 4000 units daily, supported by US, may be an option for selected patients.