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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, SCOPUS: ar.j, info:eu-repo/semantics/published

Background: The primary aim was to explore the concept of isolated and combined threshold-insults for brain tissue oxygenation (pbtO(2)) in relation to outcome in traumatic brain injury (TBI). Methods: A total of 239 TBI patients with data on clinical outcome (GOS) and intracranial pressure (ICP) and pbtO(2) monitoring for at least 12 h, who had been treated at the neurocritical care unit, Addenbrooke's Hospital, Cambridge, UK, between 2002 and 2022 were included. Outcome was dichotomised into favourable/unfavourable (GOS 4-5/1-3) and survival/mortality (GOS 2-5/1). PbtO(2) was studied over the entire monitoring period. Thresholds were analysed in relation to outcome based on median and mean values, percentage of time and dose per hour below critical values and visualised as the combined insult intensity and duration. Results: Median pbtO(2) was slightly, but not significantly, associated with outcome. A pbtO(2) threshold at 25 and 20 mmHg, respectively, yielded the highest x(2) when dichotomised for favourable/unfavourable outcome and mortality/survival in chi-square analyses. A higher dose and higher percentage of time spent with pbtO(2) below 25 mmHg as well as lower thresholds were associated with unfavourable outcome, but not mortality. In a combined insult intensity and duration analysis, there was a transition from favourable towards unfavourable outcome when pbtO(2) went below 25-30 mmHg for 30 min and similar transitions occurred for shorter durations when the intensity was higher. Although these insults were rare, pbtO(2) under 15 mmHg was more strongly associated with unfavourable outcome if, concurrently, ICP was above 20 mmHg, cerebral perfusion pressure below 60 mmHg, or pressure reactivity index above 0.30 than if these variables were not deranged. In a multiple logistic regression, a higher percentage of monitoring time with pbtO(2) < 15 mmHg was associated with a higher rate of unfavourable outcome. Conclusions: Low pbtO(2), under 25 mmHg and par

Background: The primary aim was to explore the concept of isolated and combined threshold-insults for brain tissue oxygenation (pbtO(2)) in relation to outcome in traumatic brain injury (TBI). Methods: A total of 239 TBI patients with data on clinical outcome (GOS) and intracranial pressure (ICP) and pbtO(2) monitoring for at least 12 h, who had been treated at the neurocritical care unit, Addenbrooke's Hospital, Cambridge, UK, between 2002 and 2022 were included. Outcome was dichotomised into favourable/unfavourable (GOS 4-5/1-3) and survival/mortality (GOS 2-5/1). PbtO(2) was studied over the entire monitoring period. Thresholds were analysed in relation to outcome based on median and mean values, percentage of time and dose per hour below critical values and visualised as the combined insult intensity and duration. Results: Median pbtO(2) was slightly, but not significantly, associated with outcome. A pbtO(2) threshold at 25 and 20 mmHg, respectively, yielded the highest x(2) when dichotomised for favourable/unfavourable outcome and mortality/survival in chi-square analyses. A higher dose and higher percentage of time spent with pbtO(2) below 25 mmHg as well as lower thresholds were associated with unfavourable outcome, but not mortality. In a combined insult intensity and duration analysis, there was a transition from favourable towards unfavourable outcome when pbtO(2) went below 25-30 mmHg for 30 min and similar transitions occurred for shorter durations when the intensity was higher. Although these insults were rare, pbtO(2) under 15 mmHg was more strongly associated with unfavourable outcome if, concurrently, ICP was above 20 mmHg, cerebral perfusion pressure below 60 mmHg, or pressure reactivity index above 0.30 than if these variables were not deranged. In a multiple logistic regression, a higher percentage of monitoring time with pbtO(2) < 15 mmHg was associated with a higher rate of unfavourable outcome. Conclusions: Low pbtO(2), under 25 mmHg and par

Background: The primary aim was to explore the concept of isolated and combined threshold-insults for brain tissue oxygenation (pbtO(2)) in relation to outcome in traumatic brain injury (TBI). Methods: A total of 239 TBI patients with data on clinical outcome (GOS) and intracranial pressure (ICP) and pbtO(2) monitoring for at least 12 h, who had been treated at the neurocritical care unit, Addenbrooke's Hospital, Cambridge, UK, between 2002 and 2022 were included. Outcome was dichotomised into favourable/unfavourable (GOS 4-5/1-3) and survival/mortality (GOS 2-5/1). PbtO(2) was studied over the entire monitoring period. Thresholds were analysed in relation to outcome based on median and mean values, percentage of time and dose per hour below critical values and visualised as the combined insult intensity and duration. Results: Median pbtO(2) was slightly, but not significantly, associated with outcome. A pbtO(2) threshold at 25 and 20 mmHg, respectively, yielded the highest x(2) when dichotomised for favourable/unfavourable outcome and mortality/survival in chi-square analyses. A higher dose and higher percentage of time spent with pbtO(2) below 25 mmHg as well as lower thresholds were associated with unfavourable outcome, but not mortality. In a combined insult intensity and duration analysis, there was a transition from favourable towards unfavourable outcome when pbtO(2) went below 25-30 mmHg for 30 min and similar transitions occurred for shorter durations when the intensity was higher. Although these insults were rare, pbtO(2) under 15 mmHg was more strongly associated with unfavourable outcome if, concurrently, ICP was above 20 mmHg, cerebral perfusion pressure below 60 mmHg, or pressure reactivity index above 0.30 than if these variables were not deranged. In a multiple logistic regression, a higher percentage of monitoring time with pbtO(2) < 15 mmHg was associated with a higher rate of unfavourable outcome. Conclusions: Low pbtO(2), under 25 mmHg and par

PURPOSE: Massage therapy is an important adjunctive treatment for physiologic and psychologic symptoms and has been shown to benefit patients among a wide variety of patient populations. SETTING: Few studies have investigated the utility of massage therapy in the general ICU setting, and even fewer have done so in the neurological ICU (NeuroICU). RESEARCH DESIGN: If massage therapy was determined to improve objective outcomes-or even subjective outcomes in the absence of harm-massage may be more readily employed as a complementary therapy, particularly in the ICU setting or in patients with acute neurological injury. INTERVENTION: This pilot study aimed to assess the safety of massage in the neurocritical care unit and its impact on patient vital signs, subjective pain assessment, and other clinical outcomes. PARTICIPANTS: Twenty-one patients who received massage therapy during admission to the neurocritical care service were compared to matched controls in a retrospective case control study design. RESULTS: We found a statistically significant reduction in pain scores among patients with acute neurological injury who received massage therapy. There was no statistical difference in hospital length of stay, discharge destination, in-hospital mortality, adverse events, or incidence/duration of delirium between patients who received massage therapy and those who did not. No adverse events were ascribed to the massage therapy when evaluated by blinded neurocritical care specialists. CONCLUSION: This study found that massage therapy may be safe for many patients in the NeuroICU and may offer additional subjective benefits.

Targeted temperature management (TTM) is standard of care for neonatal hypoxic ischemic encephalopathy (HIE). Prevention of fever, not excluding cooling core body temperature to 33°C, is standard of care for brain injury post cardiac arrest. Although TTM is beneficial, HIE and cardiac arrest still carry significant risk of death and severe disability. Mammalian hibernation is a gold standard of neuroprotective metabolic suppression, that if better understood might make TTM more accessible, improve efficacy of TTM and identify adjunctive therapies to protect and regenerate neurons after hypoxic ischemia brain injury. Hibernating species tolerate cerebral ischemia/reperfusion better than humans and better than other models of cerebral ischemia tolerance. Such tolerance limits risk of transitions into and out of hibernation torpor and suggests that a barrier to translate hibernation torpor may be human vulnerability to these transitions. At the same time, understanding how hibernating mammals protect their brains is an opportunity to identify adjunctive therapies for TTM. Here we summarize what is known about the hemodynamics of hibernation and how the hibernating brain resists injury to identify opportunities to translate these mechanisms for neurocritical care.

Background: The primary aim was to explore the concept of isolated and combined threshold-insults for brain tissue oxygenation (pbtO(2)) in relation to outcome in traumatic brain injury (TBI). Methods: A total of 239 TBI patients with data on clinical outcome (GOS) and intracranial pressure (ICP) and pbtO(2) monitoring for at least 12 h, who had been treated at the neurocritical care unit, Addenbrooke's Hospital, Cambridge, UK, between 2002 and 2022 were included. Outcome was dichotomised into favourable/unfavourable (GOS 4-5/1-3) and survival/mortality (GOS 2-5/1). PbtO(2) was studied over the entire monitoring period. Thresholds were analysed in relation to outcome based on median and mean values, percentage of time and dose per hour below critical values and visualised as the combined insult intensity and duration. Results: Median pbtO(2) was slightly, but not significantly, associated with outcome. A pbtO(2) threshold at 25 and 20 mmHg, respectively, yielded the highest x(2) when dichotomised for favourable/unfavourable outcome and mortality/survival in chi-square analyses. A higher dose and higher percentage of time spent with pbtO(2) below 25 mmHg as well as lower thresholds were associated with unfavourable outcome, but not mortality. In a combined insult intensity and duration analysis, there was a transition from favourable towards unfavourable outcome when pbtO(2) went below 25-30 mmHg for 30 min and similar transitions occurred for shorter durations when the intensity was higher. Although these insults were rare, pbtO(2) under 15 mmHg was more strongly associated with unfavourable outcome if, concurrently, ICP was above 20 mmHg, cerebral perfusion pressure below 60 mmHg, or pressure reactivity index above 0.30 than if these variables were not deranged. In a multiple logistic regression, a higher percentage of monitoring time with pbtO(2) < 15 mmHg was associated with a higher rate of unfavourable outcome. Conclusions: Low pbtO(2), under 25 mmHg and par

BACKGROUND: Intracranial pressure (ICP) monitoring is widely practiced, but the indications are incompletely developed, and guidelines are poorly followed. OBJECTIVE: To study the monitoring practices of an established expert panel (the clinical working group from the Seattle International Brain Injury Consensus Conference effort) to examine the match between monitoring guidelines and their clinical decision-making and offer guidance for clinicians considering monitor insertion. METHODS: We polled the 42 Seattle International Brain Injury Consensus Conference panel members' ICP monitoring decisions for virtual patients, using matrices of presenting signs (Glasgow Coma Scale [GCS] total or GCS motor, pupillary examination, and computed tomography diagnosis). Monitor insertion decisions were yes, no, or unsure (traffic light approach). We analyzed their responses for weighting of the presenting signs in decision-making using univariate regression. RESULTS: Heatmaps constructed from the choices of 41 panel members revealed wider ICP monitor use than predicted by guidelines. Clinical examination (GCS) was by far the most important characteristic and differed from guidelines in being nonlinear. The modified Marshall computed tomography classification was second and pupils third. We constructed a heatmap and listed the main clinical determinants representing 80% ICP monitor insertion consensus for our recommendations. CONCLUSION: Candidacy for ICP monitoring exceeds published indicators for monitor insertion, suggesting the clinical perception that the value of ICP data is greater than simply detecting and monitoring severe intracranial hypertension. Monitor insertion heatmaps are offered as potential guidance for ICP monitor insertion and to stimulate research into what actually drives monitor insertion in unconstrained, real-world conditions.

Background: The primary aim was to explore the concept of isolated and combined threshold-insults for brain tissue oxygenation (pbtO(2)) in relation to outcome in traumatic brain injury (TBI). Methods: A total of 239 TBI patients with data on clinical outcome (GOS) and intracranial pressure (ICP) and pbtO(2) monitoring for at least 12 h, who had been treated at the neurocritical care unit, Addenbrooke's Hospital, Cambridge, UK, between 2002 and 2022 were included. Outcome was dichotomised into favourable/unfavourable (GOS 4-5/1-3) and survival/mortality (GOS 2-5/1). PbtO(2) was studied over the entire monitoring period. Thresholds were analysed in relation to outcome based on median and mean values, percentage of time and dose per hour below critical values and visualised as the combined insult intensity and duration. Results: Median pbtO(2) was slightly, but not significantly, associated with outcome. A pbtO(2) threshold at 25 and 20 mmHg, respectively, yielded the highest x(2) when dichotomised for favourable/unfavourable outcome and mortality/survival in chi-square analyses. A higher dose and higher percentage of time spent with pbtO(2) below 25 mmHg as well as lower thresholds were associated with unfavourable outcome, but not mortality. In a combined insult intensity and duration analysis, there was a transition from favourable towards unfavourable outcome when pbtO(2) went below 25-30 mmHg for 30 min and similar transitions occurred for shorter durations when the intensity was higher. Although these insults were rare, pbtO(2) under 15 mmHg was more strongly associated with unfavourable outcome if, concurrently, ICP was above 20 mmHg, cerebral perfusion pressure below 60 mmHg, or pressure reactivity index above 0.30 than if these variables were not deranged. In a multiple logistic regression, a higher percentage of monitoring time with pbtO(2) < 15 mmHg was associated with a higher rate of unfavourable outcome. Conclusions: Low pbtO(2), under 25 mmHg and par

Background: Acute brain injured (ABI) patients are at high risk of developing ventilator-associated pneumonia (VAP). However, incidence, risk factors and effects on outcome of VAP are not completely elucidated in this population. The primary aim of this study was to determine the incidence of VAP in a cohort of ABI patients. The secondary objectives included the identification of risk factors for development of VAP, and the impact of VAP on clinical outcomes. Clinical outcomes were defined as intensive care unit length of stay (ICU-LOS), duration of invasive mechanical ventilation (IMV), and ICU mortality. Methods: Pre-planned sub-analysis of the Extubation strategies in Neuro-Intensive care unit (ICU) patients and associations with Outcomes (ENIO) international multi-center prospective observational study. Patients with available data on VAP, who received at least 48 h of IMV and ICU-LOS ≥ 72 h were included. Results: Out of 1512 patients included in the ENIO study, 1285 were eligible for this analysis. The prevalence of VAP was 39.5% (33.7 cases /1000 ventilator-days), with a high heterogeneity across countries and according to the type of brain injury. VAP was significantly more frequent in male patients, in those with smoke habits and when intraparenchymal probe (IP), external ventricular drain (EVD) or hypothermia (p < 0.001) were used. Independent risk factors for VAP occurrence were male gender, the use of IP, hypothermia, and the occurrence of tracheobronchitis during ICU stay. VAP was not an independent risk factor for ICU mortality (Hazard Ratio, HR = 0.71 95%CI 0.43–1.16, p = 0.168), but was independently associated with longer ICU stay (OR = 2.55 95%CI 2.01–3.23, p < 0.001). Conclusions: VAP is common in ABI patients. Male gender, IP and EVD insertion, tracheobronchitis, and the use of therapeutic hypothermia were significantly associated with VAP occurrence. VAP did not affect mortality but increased ICU-LOS., SCOPUS: ar.j, info:eu-repo/semantics/published

[EN] Background Levetiracetam pharmacokinetics is extensively altered in critically ill patients with augmented renal clearance (ARC). Consequently, the dosage regimens commonly used in clinical practice may not be sufficient to achieve target plasma concentrations. The aim of this study is to propose alternative dosage regimens able to achieve target concentrations in this population. Furthermore, the feasibility of the proposed dosing regimens will be discussed from a clinical point of view. Methods Different dosage regimens for levetiracetam were evaluated in critically ill patients with ARC. Monte Carlo simulations were conducted with extended or continuous infusions and/or high drug doses using a previously developed population pharmacokinetic model. To assess the clinical feasibility of the proposed dosages, we carried out a literature search to evaluate the information on toxicity and efficacy of continuous administration or high doses, as well as the post-dilution stability of levetiracetam. Results According to the simulations, target concentrations in patients with CrCl of 160 or 200 mL/min can be achieved with the 3000 mg daily dose by prolonging the infusion time of levetiracetam. For patients with CrCl of 240 mL/min, it would be necessary to administer doses higher than the maximum recommended. Available evidence suggests that levetiracetam administration in continuous infusion or at higher doses than those approved seems to be safe. It would be desirable to re-examinate the current recommendations about drug stability and to achieve a consensus in this issue. Conclusions Conventional dosage regimens of levetiracetam (500-1500 mg twice daily in a short infusion) do not allow obtaining drug plasma concentrations among the defined target in critically ill patients with ARC. Therefore, new dosing guidelines with specific recommendations for patients in this subpopulation are needed. This study proposes new dosages for levetiracetam, including extended (4 o

[EN] Background Levetiracetam pharmacokinetics is extensively altered in critically ill patients with augmented renal clearance (ARC). Consequently, the dosage regimens commonly used in clinical practice may not be sufficient to achieve target plasma concentrations. The aim of this study is to propose alternative dosage regimens able to achieve target concentrations in this population. Furthermore, the feasibility of the proposed dosing regimens will be discussed from a clinical point of view. Methods Different dosage regimens for levetiracetam were evaluated in critically ill patients with ARC. Monte Carlo simulations were conducted with extended or continuous infusions and/or high drug doses using a previously developed population pharmacokinetic model. To assess the clinical feasibility of the proposed dosages, we carried out a literature search to evaluate the information on toxicity and efficacy of continuous administration or high doses, as well as the post-dilution stability of levetiracetam. Results According to the simulations, target concentrations in patients with CrCl of 160 or 200 mL/min can be achieved with the 3000 mg daily dose by prolonging the infusion time of levetiracetam. For patients with CrCl of 240 mL/min, it would be necessary to administer doses higher than the maximum recommended. Available evidence suggests that levetiracetam administration in continuous infusion or at higher doses than those approved seems to be safe. It would be desirable to re-examinate the current recommendations about drug stability and to achieve a consensus in this issue. Conclusions Conventional dosage regimens of levetiracetam (500-1500 mg twice daily in a short infusion) do not allow obtaining drug plasma concentrations among the defined target in critically ill patients with ARC. Therefore, new dosing guidelines with specific recommendations for patients in this subpopulation are needed. This study proposes new dosages for levetiracetam, including extended (4 o

Although seizures in neonates are common and often due to acute brain injury, 10-15% are unprovoked from congenital brain malformations. A better understanding of the risk of neonatal-onset epilepsy by the type of brain malformation is essential for counseling and monitoring. In this retrospective cohort study, we evaluated 132 neonates with congenital brain malformations and their risk of neonatal-onset epilepsy. Malformations were classified into one of five categories based on imaging patterns on prenatal or postnatal imaging. Infants were monitored with continuous video EEG (cEEG) for encephalopathy and paroxysmal events in addition to abnormal neuroimaging. Seventy-four of 132 (56%) neonates underwent EEG monitoring, and 18 of 132 (14%) were diagnosed with neonatal-onset epilepsy. The highest prevalence of epilepsy was in neonates with disorders of neuronal migration/organization (9/34, 26%; 95% confidence interval [CI] = 13-44%), followed by disorders of early prosencephalic development (6/38, 16%; 95% CI = 6-31%), complex total brain malformations (2/16, 13%; 95% CI = 2-38%), and disorders of midbrain/hindbrain malformations (1/30, 3%; 95% CI = 0-17%). Of neonates with epilepsy, 5 of 18 (28%) had only electrographic seizures, 13 of 18 (72%) required treatment with two or more antiseizure medicines (ASMs), and 7 of 18 (39%) died within the neonatal period. Our results demonstrate that disorders of neuronal migration/organization represent the highest-risk group for early-onset epilepsy. Seizures are frequently electrographic only, require treatment with multiple ASMs, and portend a high mortality rate. These results support American Clinical Neurophysiology Society recommendations for EEG monitoring during the neonatal period for infants with congenital brain malformations.

We sought to characterize intracranial hemorrhage (ICH) as a seizure etiology in infants born term and preterm. For infants born term, we sought to compare seizure severity and treatment response for multisite vs single-site ICH and hypoxic-ischemic encephalopathy (HIE) with vs without ICH. We studied 112 newborn infants with seizures attributed to ICH and 201 infants born at term with seizures attributed to HIE, using a cohort of consecutive infants with clinically diagnosed and/or electrographic seizures prospectively enrolled in the multicenter Neonatal Seizure Registry. We compared seizure severity and treatment response among infants with complicated ICH, defined as multisite vs single-site ICH and HIE with vs without ICH. ICH was a more common seizure etiology in infants born preterm vs term (27% vs 10%, P < .001). Most infants had subclinical seizures (74%) and an incomplete response to initial antiseizure medication (ASM) (68%). In infants born term, multisite ICH was associated with more subclinical seizures than single-site ICH (93% vs 66%, P = .05) and an incomplete response to the initial ASM (100% vs 66%, P = .02). Status epilepticus was more common in HIE with ICH vs HIE alone (38% vs 17%, P = .05). Seizure severity was greater and treatment response was lower among infants born term with complicated ICH. These data support the use of continuous video electroencephalogram monitoring to accurately detect seizures and a multistep treatment plan that considers early use of multiple ASMs, particularly with parenchymal and high-grade intraventricular hemorrhage and complicated ICH.

BackgroundSpinal granulomas form from infectious or noninfectious inflammatory processes and are rarely present intradurally. Intradural granulomas secondary to hematoma are unreported in the literature and present diagnostic and management challenges.ObservationsA 70-year-old man receiving aspirin presented with encephalopathy, subacute malaise, and right lower extremity weakness and was diagnosed with polysubstance withdrawal and refractory hypertension requiring extended treatment. Seven days after admission, he reported increased bilateral lower extremity (BLE) weakness. Magnetic resonance imaging showed T2-3 and T7-8 masses abutting the pia, with spinal cord compression at T2-3. He was transferred to the authors' institution, and work-up showed no vascular shunting or malignancy. He underwent T2-3 laminectomies for biopsy/resection. A firm, xanthochromic mass was resected en bloc. Pathology showed organizing hematoma without infection, vascular malformation, or malignancy. Subsequent coagulopathy work-up was unremarkable. His BLE strength significantly improved, and he declined resection of the inferior mass. He completed physical therapy and was cleared for placement in a skilled nursing facility.LessonsSpinal granulomas can mimic vascular lesions and malignancy. The authors present the first report of paraparesis caused by intradural granuloma secondary to organizing hematoma, preceded by severe refractory hypertension. Tissue diagnosis is critical, and resection is curative. These findings can inform the vigilant clinician for expeditious treatment.

BackgroundCerebral microdialysis enables monitoring of brain metabolism and can be an important part of multimodal monitoring strategies in a variety of brain injuries. Microdialysis catheters can be placed in brain parenchyma through a burr hole, a cranial bolt, or directly at the time of an open craniotomy or craniectomy. The location of catheters in relation to brain pathology is important to the interpretation of data and guidance of interventions.MethodsHere we retrospectively review the use of cerebral microdialysis at a US Regional Medical Center between March 2018 and February 2022 and provide detailed descriptions and technical nuances of the different methods to place microdialysis catheters.ResultsEighty two unique microdialysis catheters were utilized in 52 patients. 35 (42.68%) were placed via a quad-lumen bolt and 47 (57.32%) were placed through craniotomies. 27 catheters (32.93%) were placed in a perilesional location, 50 (60.98%) were located in healthy tissue, and 6 (7.32%) were mispositioned. No significant difference was seen between placement by bolt or craniotomy in regard to perilesional location, mispositioning, or complications.ConclusionWith careful planning and thoughtful execution, cerebral microdialysis catheters can be successfully placed though a variety of strategies to optimize and individualize brain monitoring in different clinical settings. This paper provides a detailed guide for the various methods of catheter placement to help providers begin or expand their use of cerebral microdialysis.

[EN] Background Levetiracetam pharmacokinetics is extensively altered in critically ill patients with augmented renal clearance (ARC). Consequently, the dosage regimens commonly used in clinical practice may not be sufficient to achieve target plasma concentrations. The aim of this study is to propose alternative dosage regimens able to achieve target concentrations in this population. Furthermore, the feasibility of the proposed dosing regimens will be discussed from a clinical point of view. Methods Different dosage regimens for levetiracetam were evaluated in critically ill patients with ARC. Monte Carlo simulations were conducted with extended or continuous infusions and/or high drug doses using a previously developed population pharmacokinetic model. To assess the clinical feasibility of the proposed dosages, we carried out a literature search to evaluate the information on toxicity and efficacy of continuous administration or high doses, as well as the post-dilution stability of levetiracetam. Results According to the simulations, target concentrations in patients with CrCl of 160 or 200 mL/min can be achieved with the 3000 mg daily dose by prolonging the infusion time of levetiracetam. For patients with CrCl of 240 mL/min, it would be necessary to administer doses higher than the maximum recommended. Available evidence suggests that levetiracetam administration in continuous infusion or at higher doses than those approved seems to be safe. It would be desirable to re-examinate the current recommendations about drug stability and to achieve a consensus in this issue. Conclusions Conventional dosage regimens of levetiracetam (500-1500 mg twice daily in a short infusion) do not allow obtaining drug plasma concentrations among the defined target in critically ill patients with ARC. Therefore, new dosing guidelines with specific recommendations for patients in this subpopulation are needed. This study proposes new dosages for levetiracetam, including extended (4 o

OBJECTIVES: To describe the changes in ventilator management over time in patients with neurologic disease at ICU admission and to estimate factors associated with 28-day hospital mortality. DESIGN: Secondary analysis of three prospective, observational, multicenter studies. SETTING: Cohort studies conducted in 2004, 2010, and 2016. PATIENTS: Adult patients who received mechanical ventilation for more than 12 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among the 20,929 patients enrolled, we included 4,152 (20%) mechanically ventilated patients due to different neurologic diseases. Hemorrhagic stroke and brain trauma were the most common pathologies associated with the need for mechanical ventilation. Although volume-cycled ventilation remained the preferred ventilation mode, there was a significant (p < 0.001) increment in the use of pressure support ventilation. The proportion of patients receiving a protective lung ventilation strategy was increased over time: 47% in 2004, 63% in 2010, and 65% in 2016 (p < 0.001), as well as the duration of protective ventilation strategies: 406 days per 1,000 mechanical ventilation days in 2004, 523 days per 1,000 mechanical ventilation days in 2010, and 585 days per 1,000 mechanical ventilation days in 2016 (p < 0.001). There were no differences in the length of stay in the ICU, mortality in the ICU, and mortality in hospital from 2004 to 2016. Independent risk factors for 28-day mortality were age greater than 75 years, Simplified Acute Physiology Score II greater than 50, the occurrence of organ dysfunction within first 48 hours after brain injury, and specific neurologic diseases such as hemorrhagic stroke, ischemic stroke, and brain trauma. CONCLUSIONS: More lung-protective ventilatory strategies have been implemented over years in neurologic patients with no effect on pulmonary complications or on survival. We found several prognostic factors on mortality such as advanced age, the severity of the

IntroductionNeurocritical care focuses on the care of critically ill patients with an acute neurologic disorder and has grown significantly in the past few years. However, there is a lack of data that describe the scope of practice of neurointensivists and epidemiological data on the types of patients and treatments used in neurocritical care units worldwide. To address these issues, we designed a multicenter, international, point-prevalence, cross-sectional, prospective, observational, non-interventional study in the setting of neurocritical care (PRINCE Study).MethodsIn this manuscript, we analyzed data from the initial phase of the study that included registration, hospital, and intensive care unit (ICU) organizations. We present here descriptive statistics to summarize data from the registration case report form. We performed the Kruskal-Wallis test followed by the Dunn procedure to test for differences in practices among world regions.ResultsWe analyzed information submitted by 257 participating sites from 47 countries. The majority of those sites, 119 (46.3%), were in North America, 44 (17.2%) in Europe, 34 (13.3%) in Asia, 9 (3.5%) in the Middle East, 34 (13.3%) in Latin America, and 14 (5.5%) in Oceania. Most ICUs are from academic institutions (73.4%) located in large urban centers (44% > 1 million inhabitants). We found significant differences in hospital and ICU organization, resource allocation, and use of patient management protocols. The highest nursing/patient ratio was in Oceania (100% 1:1). Dedicated Advanced Practiced Providers are mostly present in North America (73.7%) and are uncommon in Oceania (7.7%) and the Middle East (0%). The presence of dedicated respiratory therapist is common in North America (85%), Middle East (85%), and Latin America (84%) but less common in Europe (26%) and Oceania (7.7%). The presence of dedicated pharmacist is highest in North America (89%) and Oceania (85%) and least common in Latin America (38%). The majority

INTRODUCTION: Neurocritical care focuses on the care of critically ill patients with an acute neurologic disorder and has grown significantly in the past few years. However, there is a lack of data that describe the scope of practice of neurointensivists and epidemiological data on the types of patients and treatments used in neurocritical care units worldwide. To address these issues, we designed a multicenter, international, point-prevalence, cross-sectional, prospective, observational, non-interventional study in the setting of neurocritical care (PRINCE Study). METHODS: In this manuscript, we analyzed data from the initial phase of the study that included registration, hospital, and intensive care unit (ICU) organizations. We present here descriptive statistics to summarize data from the registration case report form. We performed the Kruskal-Wallis test followed by the Dunn procedure to test for differences in practices among world regions. RESULTS: We analyzed information submitted by 257 participating sites from 47 countries. The majority of those sites, 119 (46.3%), were in North America, 44 (17.2%) in Europe, 34 (13.3%) in Asia, 9 (3.5%) in the Middle East, 34 (13.3%) in Latin America, and 14 (5.5%) in Oceania. Most ICUs are from academic institutions (73.4%) located in large urban centers (44% > 1 million inhabitants). We found significant differences in hospital and ICU organization, resource allocation, and use of patient management protocols. The highest nursing/patient ratio was in Oceania (100% 1:1). Dedicated Advanced Practiced Providers are mostly present in North America (73.7%) and are uncommon in Oceania (7.7%) and the Middle East (0%). The presence of dedicated respiratory therapist is common in North America (85%), Middle East (85%), and Latin America (84%) but less common in Europe (26%) and Oceania (7.7%). The presence of dedicated pharmacist is highest in North America (89%) and Oceania (85%) and least common in Latin America (38%). The majo

Impaired cerebrovascular reactivity in adult moderate and severe traumatic brain injury (TBI) is known to be associated with worse global outcome at 6-12 months. As technology has improved over the past decades, monitoring of cerebrovascular reactivity has shifted from intermittent measures, to experimentally validated continuously updating indices at the bedside. Such advances have led to the exploration of individualised physiologic targets in adult TBI management, such as optimal cerebral perfusion pressure (CPP) values, or CPP limits in which vascular reactivity is relatively intact. These targets have been shown to have a stronger association with outcome compared with existing consensus-based guideline thresholds in severe TBI care. This has sparked ongoing prospective trials of such personalised medicine approaches in adult TBI. In this narrative review paper, we focus on the concept of cerebral autoregulation, proposed mechanisms of control and methods of continuous monitoring used in TBI. We highlight multimodal cranial monitoring approaches for continuous cerebrovascular reactivity assessment, physiologic and neuroimaging correlates, and associations with outcome. Finally, we explore the recent 'state-of-the-art' advances in personalised physiologic targets based on continuous cerebrovascular reactivity monitoring, their benefits, and implications for future avenues of research in TBI.

BACKGROUND: Neonatal seizures are associated with death and neurological morbidity; however, little is known about how neonates with seizures die. METHODS: This was a prospective, observational cohort study of neonates with seizures treated at seven sites of the Neonatal Seizure Registry. We characterized the mode of death, evaluated the association between infant characteristics and mode of death, and evaluated predictors of death or transfer to hospice. RESULTS: We enrolled 611 consecutive neonates with seizures, and 90 neonates (15%) died before hospital discharge at a median age of 11 days (range: 1 to 163 days); 32 (36%) died in the first postnatal week. An additional 19 neonates (3%) were transferred to hospice. The most common mode of in-hospital death was death after extubation amidst concerns for poor neurological prognosis, in the absence of life-threatening physiologic instability (n = 43, 48%). Only one infant died while actively receiving cardiopulmonary resuscitation. In an adjusted analysis, premature birth (odds ratio: 3.06, 95% confidence interval 1.59 to 5.90) and high seizure burden (odds ratio: 4.33, 95% confidence interval 1.88 to 9.95) were associated with increased odds of death or transfer to hospice. CONCLUSION: In a cohort of neonates with seizures, death occurred predominantly after decisions to withdraw or withhold life-sustaining intervention(s). Future work should characterize how these decisions occur and develop optimized approaches to support families and clinicians caring for newborns with seizures.

IntroductionNeurocritical care focuses on the care of critically ill patients with an acute neurologic disorder and has grown significantly in the past few years. However, there is a lack of data that describe the scope of practice of neurointensivists and epidemiological data on the types of patients and treatments used in neurocritical care units worldwide. To address these issues, we designed a multicenter, international, point-prevalence, cross-sectional, prospective, observational, non-interventional study in the setting of neurocritical care (PRINCE Study).MethodsIn this manuscript, we analyzed data from the initial phase of the study that included registration, hospital, and intensive care unit (ICU) organizations. We present here descriptive statistics to summarize data from the registration case report form. We performed the Kruskal-Wallis test followed by the Dunn procedure to test for differences in practices among world regions.ResultsWe analyzed information submitted by 257 participating sites from 47 countries. The majority of those sites, 119 (46.3%), were in North America, 44 (17.2%) in Europe, 34 (13.3%) in Asia, 9 (3.5%) in the Middle East, 34 (13.3%) in Latin America, and 14 (5.5%) in Oceania. Most ICUs are from academic institutions (73.4%) located in large urban centers (44% > 1 million inhabitants). We found significant differences in hospital and ICU organization, resource allocation, and use of patient management protocols. The highest nursing/patient ratio was in Oceania (100% 1:1). Dedicated Advanced Practiced Providers are mostly present in North America (73.7%) and are uncommon in Oceania (7.7%) and the Middle East (0%). The presence of dedicated respiratory therapist is common in North America (85%), Middle East (85%), and Latin America (84%) but less common in Europe (26%) and Oceania (7.7%). The presence of dedicated pharmacist is highest in North America (89%) and Oceania (85%) and least common in Latin America (38%). The majority

BackgroundAcute treatment of cerebral edema and elevated intracranial pressure is a common issue in patients with neurological injury. Practical recommendations regarding selection and monitoring of therapies for initial management of cerebral edema for optimal efficacy and safety are generally lacking. This guideline evaluates the role of hyperosmolar agents (mannitol, HTS), corticosteroids, and selected non-pharmacologic therapies in the acute treatment of cerebral edema. Clinicians must be able to select appropriate therapies for initial cerebral edema management based on available evidence while balancing efficacy and safety.MethodsThe Neurocritical Care Society recruited experts in neurocritical care, nursing, and pharmacy to create a panel in 2017. The group generated 16 clinical questions related to initial management of cerebral edema in various neurological insults using the PICO format. A research librarian executed a comprehensive literature search through July 2018. The panel screened the identified articles for inclusion related to each specific PICO question and abstracted necessary information for pertinent publications. The panel used GRADE methodology to categorize the quality of evidence as high, moderate, low, or very low based on their confidence that the findings of each publication approximate the true effect of the therapy.ResultsThe panel generated recommendations regarding initial management of cerebral edema in neurocritical care patients with subarachnoid hemorrhage, traumatic brain injury, acute ischemic stroke, intracerebral hemorrhage, bacterial meningitis, and hepatic encephalopathy.ConclusionThe available evidence suggests hyperosmolar therapy may be helpful in reducing ICP elevations or cerebral edema in patients with SAH, TBI, AIS, ICH, and HE, although neurological outcomes do not appear to be affected. Corticosteroids appear to be helpful in reducing cerebral edema in patients with bacterial meningitis, but not ICH. Differences in

Impaired cerebrovascular reactivity in adult moderate and severe traumatic brain injury (TBI) is known to be associated with worse global outcome at 6-12 months. As technology has improved over the past decades, monitoring of cerebrovascular reactivity has shifted from intermittent measures, to experimentally validated continuously updating indices at the bedside. Such advances have led to the exploration of individualised physiologic targets in adult TBI management, such as optimal cerebral perfusion pressure (CPP) values, or CPP limits in which vascular reactivity is relatively intact. These targets have been shown to have a stronger association with outcome compared with existing consensus-based guideline thresholds in severe TBI care. This has sparked ongoing prospective trials of such personalised medicine approaches in adult TBI. In this narrative review paper, we focus on the concept of cerebral autoregulation, proposed mechanisms of control and methods of continuous monitoring used in TBI. We highlight multimodal cranial monitoring approaches for continuous cerebrovascular reactivity assessment, physiologic and neuroimaging correlates, and associations with outcome. Finally, we explore the recent 'state-of-the-art' advances in personalised physiologic targets based on continuous cerebrovascular reactivity monitoring, their benefits, and implications for future avenues of research in TBI.

BACKGROUND: Neonatal seizures are associated with death and neurological morbidity; however, little is known about how neonates with seizures die. METHODS: This was a prospective, observational cohort study of neonates with seizures treated at seven sites of the Neonatal Seizure Registry. We characterized the mode of death, evaluated the association between infant characteristics and mode of death, and evaluated predictors of death or transfer to hospice. RESULTS: We enrolled 611 consecutive neonates with seizures, and 90 neonates (15%) died before hospital discharge at a median age of 11 days (range: 1 to 163 days); 32 (36%) died in the first postnatal week. An additional 19 neonates (3%) were transferred to hospice. The most common mode of in-hospital death was death after extubation amidst concerns for poor neurological prognosis, in the absence of life-threatening physiologic instability (n = 43, 48%). Only one infant died while actively receiving cardiopulmonary resuscitation. In an adjusted analysis, premature birth (odds ratio: 3.06, 95% confidence interval 1.59 to 5.90) and high seizure burden (odds ratio: 4.33, 95% confidence interval 1.88 to 9.95) were associated with increased odds of death or transfer to hospice. CONCLUSION: In a cohort of neonates with seizures, death occurred predominantly after decisions to withdraw or withhold life-sustaining intervention(s). Future work should characterize how these decisions occur and develop optimized approaches to support families and clinicians caring for newborns with seizures.

This report describes the successful management of a case of central neurogenic hyperventilation (CNH) refractory to high dose sedation by increasing the mechanical dead space. A 46-year-old male presented with a history of multiple neurological symptoms. Following an extensive evaluation, he was diagnosed with primary diffuse CNS lymphoma and started on high dose steroids. After initial symptomatic improvement, the patient developed increasing respiratory distress and tachypnea. He was intubated and transferred to the neurointensive care unit (neuro ICU). While in the ICU the patient remained ventilator dependent with significant tachypnea and respiratory alkalosis resistant to fentanyl and propofol. This prompted an attempt to normalize the PaCO2 via an increase of the mechanical dead space. This approach successfully increased PaCO2 and bridged the patient until ongoing therapy for the underlying disease resolved the pervasive breathing pattern typical of CNH. Further investigation is warranted to evaluate this strategy, which upon review of the literature appears underused.

This report describes the successful management of a case of central neurogenic hyperventilation (CNH) refractory to high dose sedation by increasing the mechanical dead space. A 46-year-old male presented with a history of multiple neurological symptoms. Following an extensive evaluation, he was diagnosed with primary diffuse CNS lymphoma and started on high dose steroids. After initial symptomatic improvement, the patient developed increasing respiratory distress and tachypnea. He was intubated and transferred to the neurointensive care unit (neuro ICU). While in the ICU the patient remained ventilator dependent with significant tachypnea and respiratory alkalosis resistant to fentanyl and propofol. This prompted an attempt to normalize the PaCO2 via an increase of the mechanical dead space. This approach successfully increased PaCO2 and bridged the patient until ongoing therapy for the underlying disease resolved the pervasive breathing pattern typical of CNH. Further investigation is warranted to evaluate this strategy, which upon review of the literature appears underused.

In a prospective cohort of 534 neonates with acute symptomatic seizures, 66% had incomplete response to the initial loading dose of antiseizure medication (ASM). Treatment response did not differ by gestational age, sex, medication, or dose. The risk of incomplete response was highest for seizures due to intracranial hemorrhage and lowest for hypoxic-ischemic encephalopathy, although the difference was not significant after adjusting for high seizure burden and therapeutic hypothermia treatment. Future trial design may test ASMs in neonates with all acute symptomatic seizure etiologies and could target neonates with seizures refractory to an initial ASM.

BackgroundTo explore intubation rates among patients with status epilepticus (SE) and the degree of institutional variation.MethodsSerial cross-sectional study of SE-related hospitalizations from 2004 to 2013 using data from the National Inpatient Sample. The primary outcome was intubation of patients with SE. Multivariable models identified predictors of intubation, institutional variation in intubation rates, and the proportion of variance attributable to individual hospitals. This analysis was repeated using data from 5 states in the State Inpatient Databases (SID).ResultsThere were 119 337 SE hospitalizations. The overall intubation rate was 32.7% (95% confidence interval [CI]: 32.2%-33.3%). There was marked variation in estimated intubation rates, ranging from 2% to 80% in the lowest and highest quintile after adjustment. There was somewhat less variability in the SID cohort where quintiles ranged from 10% to 54%. Those undergoing intubation were more often men and presenting with stroke, intracerebral hemorrhage, central nervous system infection, hyponatremia, and alcohol withdrawal. Urban location (odds ratio [OR]: 3.8, 95% CI: 2.7-5.5) and hospitalization at a teaching institution (OR: 3.9, 95% CI: 1.2-12.6) were even stronger predictors of intubation after adjustment for clinical factors. A regression including both patient- and hospital-level variables to predict intubation also performed better than a regression including patient factors alone (C statistic 0.81 vs 0.59, respectively).ConclusionsThere is considerable institutional variation in intubation rates for SE independent of patient characteristics suggesting that decisions around intubation rest heavily on where one is hospitalized. Further work is needed to clarify how this variation influences outcomes.

The 2018 Paris Intensive Care symposium entitled “Update in Neurocritical Care” was organized in Paris, June 21–22, 2018, under the auspices of the French Intensive Care Society. This 2-day post-graduate educational symposium comprised several chapters, aiming first to provide all-board intensivists with current standards for the clinical assessment of altered consciousness states (including coma and delirium) and peripheral nervous system in critically ill patients, monitoring of brain function (specifically, electro-encephalography) and best practices for sedation—analgesia—delirium management. An update on the treatment of specific severe brain pathologies—including ischaemic/haemorrhagic stroke, cerebral venous thrombosis, hypoxic-ischaemic brain injury, immune-mediated and infectious encephalitis and refractory status epilepticus—was also provided. Finally, we discuss how to approach some difficult decisions, namely the role of decompressive craniectomy and prognostication models in patients with head injury. For each chapter, the scope of the present review was to provide important issues and key messages, provide most recent and relevant literature in the field, and briefly describe new developments in the field., SCOPUS: re.j, info:eu-repo/semantics/published

The 2018 Paris Intensive Care symposium entitled “Update in Neurocritical Care” was organized in Paris, June 21–22, 2018, under the auspices of the French Intensive Care Society. This 2-day post-graduate educational symposium comprised several chapters, aiming first to provide all-board intensivists with current standards for the clinical assessment of altered consciousness states (including coma and delirium) and peripheral nervous system in critically ill patients, monitoring of brain function (specifically, electro-encephalography) and best practices for sedation—analgesia—delirium management. An update on the treatment of specific severe brain pathologies—including ischaemic/haemorrhagic stroke, cerebral venous thrombosis, hypoxic-ischaemic brain injury, immune-mediated and infectious encephalitis and refractory status epilepticus—was also provided. Finally, we discuss how to approach some difficult decisions, namely the role of decompressive craniectomy and prognostication models in patients with head injury. For each chapter, the scope of the present review was to provide important issues and key messages, provide most recent and relevant literature in the field, and briefly describe new developments in the field.

Meeting Abstract: PS2.04.10

BackgroundThe Emergency Neurological Life Support (ENLS) is an educational initiative designed to improve the acute management of neurological injuries. However, the applicability of the course in low-income countries in unknown. We evaluated the impact of the course on knowledge, decision-making skills and preparedness to manage neurological emergencies in a resource-limited country.MethodsA prospective cohort study design was implemented for the first ENLS course held in Asia. Knowledge and decision-making skills for neurological emergencies were assessed at baseline, post-course and at 6 months following course completion. To determine perceived knowledge and preparedness, data were collected using surveys administered immediately post-course and 6 months later.ResultsA total of 34 acute care physicians from across Nepal attended the course. Knowledge and decision-making skills significantly improved following the course (p=0.0008). Knowledge and decision-making skills remained significantly improved after 6 months, compared with before the course (p=0.02), with no significant loss of skills immediately following the course to the 6-month follow-up (p=0.16). At 6 months, the willingness to participate in continuing medical education activities remained evident, with 77% (10/13) of participants reporting a change in their clinical practice and decision-making, with the repeated use of ENLS protocols as the main driver of change.ConclusionsUsing the ENLS framework, neurocritical care education can be delivered in low-income countries to improve knowledge uptake, with evidence of knowledge retention up to 6 months.

BACKGROUND: Optimal cerebral perfusion pressure (CPPopt) targeting in traumatic brain injury (TBI) patients constitutes an active and controversial area of research. It has been suggested that an autoregulation guided CPP therapy may improve TBI outcome. Prerequisites of a CPPopt intervention study would be objective criteria for the CPPopt detection. This study compared the agreement between automated and visual CPPopt detection. METHODS: Twenty-five clinicians from 18 centers worldwide, familiar with brain monitoring and using dedicated software, reviewed ten 4-hour CPPopt screenshots at 48 hours after ictus in selected TBI patients. Each screenshot displayed the trends of cerebral perfusion pressure (CPP), intracranial pressure (ICP), cerebrovascular pressure reactivity (PRx) as well as the "CPP-optimal" curve and its associated value (automated CPPopt). The main objective was to evaluate the agreement between expert clinicians as well as the agreement between the clinicians and automated CPPopt. RESULTS : Twenty-two clinicians responded to our call (88%). Three screenshots were judged as "CPPopt not determinable" by > 45% of the clinicians. For the whole group, the consensus between automated CPPopt and clinicians' visual CPPopt was high. Three clinicians were identified as outliers. All clinicians recommended to modify CPP when patients differed >+/- 5 mmHg from their CPPopt. The inter-observer consensus was highest in cases with current CPP below the optimal value. CONCLUSIONS: The overall agreement between automated CPPopt and visual CPPopt identified by autoregulation experts was high, except for those cases when the curve was deemed by the clinicians not reliable enough to yield a trustworthy CPPopt.

BackgroundThe Emergency Neurological Life Support (ENLS) is an educational initiative designed to improve the acute management of neurological injuries. However, the applicability of the course in low-income countries in unknown. We evaluated the impact of the course on knowledge, decision-making skills and preparedness to manage neurological emergencies in a resource-limited country.MethodsA prospective cohort study design was implemented for the first ENLS course held in Asia. Knowledge and decision-making skills for neurological emergencies were assessed at baseline, post-course and at 6 months following course completion. To determine perceived knowledge and preparedness, data were collected using surveys administered immediately post-course and 6 months later.ResultsA total of 34 acute care physicians from across Nepal attended the course. Knowledge and decision-making skills significantly improved following the course (p=0.0008). Knowledge and decision-making skills remained significantly improved after 6 months, compared with before the course (p=0.02), with no significant loss of skills immediately following the course to the 6-month follow-up (p=0.16). At 6 months, the willingness to participate in continuing medical education activities remained evident, with 77% (10/13) of participants reporting a change in their clinical practice and decision-making, with the repeated use of ENLS protocols as the main driver of change.ConclusionsUsing the ENLS framework, neurocritical care education can be delivered in low-income countries to improve knowledge uptake, with evidence of knowledge retention up to 6 months.

BACKGROUND: Optimal cerebral perfusion pressure (CPPopt) targeting in traumatic brain injury (TBI) patients constitutes an active and controversial area of research. It has been suggested that an autoregulation guided CPP therapy may improve TBI outcome. Prerequisites of a CPPopt intervention study would be objective criteria for the CPPopt detection. This study compared the agreement between automated and visual CPPopt detection. METHODS: Twenty-five clinicians from 18 centers worldwide, familiar with brain monitoring and using dedicated software, reviewed ten 4-hour CPPopt screenshots at 48 hours after ictus in selected TBI patients. Each screenshot displayed the trends of cerebral perfusion pressure (CPP), intracranial pressure (ICP), cerebrovascular pressure reactivity (PRx) as well as the "CPP-optimal" curve and its associated value (automated CPPopt). The main objective was to evaluate the agreement between expert clinicians as well as the agreement between the clinicians and automated CPPopt. RESULTS : Twenty-two clinicians responded to our call (88%). Three screenshots were judged as "CPPopt not determinable" by > 45% of the clinicians. For the whole group, the consensus between automated CPPopt and clinicians' visual CPPopt was high. Three clinicians were identified as outliers. All clinicians recommended to modify CPP when patients differed >+/- 5 mmHg from their CPPopt. The inter-observer consensus was highest in cases with current CPP below the optimal value. CONCLUSIONS: The overall agreement between automated CPPopt and visual CPPopt identified by autoregulation experts was high, except for those cases when the curve was deemed by the clinicians not reliable enough to yield a trustworthy CPPopt.

Background: Cerebral injury may alter the autoregulation of cerebral blood flow. Pressure reactivity (PR) is considered as a surrogate measure of autoregulation. Little is known whether PR is associated with measures of brain metabolism and indicators of ischemia and cell damage. We speculate that prostacyclin may affect extracellular glycerol levels (a measure of cell membrane degradation), measured by microdialysis in the brain, and thus glycerol’s association with PR. Material and Methods: The study is a randomized, double-blinded placebo-control study on the effect of prostacyclin treatment (0.5 ng/kg/min) in severe traumatic brain injury (sTBI). The basic treatment was an intracranial pressure (ICP) targeted therapy based on the Lund concept. Inclusion criteria were verified blunt head trauma, GCS£8, age 15 -70 yrs, and a first measured cerebral perfusion pressure of ‡10 mmHg. Multimodal monitoring was applied. Samples from a brain microdialysis catheter placed on the worst affected side, close to the penumbra zone, were analysed. Mean (glycerolmean) and maximal glycerol (glycerolmax) during the 96 hrs sampling period were calculated. The mean PR was calculated as the ICP/MAP regression coefficient based on hourly mean ICP and MAP (mean arterial blood pressure) during the first 96 hrs. Results: 45 patients, mean age 35.5–2.2 yrs, GCS 6 (3-8) and ISS 29 (9-50) were included. In the placebo group there was a positive correlation between glycerolmean (r=0.503, p=0.01), glycerolmax (r=0.490, p=0.015) levels and PR levels. This correlation was attenuated/abolished in the prostacyclin group. Glycerol tended to be higher and PR was higher in the placebo group (p=0.0164) as compared to the prostacyclin group. Conclusion: PR is correlated to the glycerol level in patients suffering from sTBI. Prostacyclin attenuates this correlation. Glycerol is associated with membrane degradation and may support glycerol as a biomarker for vascular endothelial breakdown. Such a breakd

Traumatic brain injury (TBI) is a multidimensional and highly complex disease commonly resulting in widespread injury to axons, due to rapid inertial acceleration/deceleration forces transmitted to the brain during impact. Axonal injury leads to brain network dysfunction, significantly contributing to cognitive and functional impairments frequently observed in TBI survivors. Diffuse axonal injury (DAI) is a clinical entity suggested by impaired level of consciousness and coma on clinical examination and characterized by widespread injury to the hemispheric white matter tracts, the corpus callosum and the brain stem. The clinical course of DAI is commonly unpredictable and it remains a challenging entity with limited therapeutic options, to date. Although axonal integrity may be disrupted at impact, the majority of axonal pathology evolves over time, resulting from delayed activation of complex intracellular biochemical cascades. Activation of these secondary biochemical pathways may lead to axonal transection, named secondary axotomy, and be responsible for the clinical decline of DAI patients. Advances in the neurocritical care of TBI patients have been achieved by refinements in multimodality monitoring for prevention and early detection of secondary injury factors, which can be applied also to DAI. There is an emerging role for biomarkers in blood, cerebrospinal fluid, and interstitial fluid using microdialysis in the evaluation of axonal injury in TBI. These biomarker studies have assessed various axonal and neuroglial markers as well as inflammatory mediators, such as cytokines and chemokines. Moreover, modern neuroimaging can detect subtle or overt DAI/white matter changes in diffuse TBI patients across all injury severities using magnetic resonance spectroscopy, diffusion tensor imaging, and positron emission tomography. Importantly, serial neuroimaging studies provide evidence for evolving axonal injury. Since axonal injury may be a key risk factor for neuro

Neurocritical care (NCC) is a branch of intensive care medicine characterized by specific physiological and biochemical monitoring techniques necessary for identifying cerebral adverse events and for evaluating specific therapies. Information is primarily obtained from physiological variables related to intracranial pressure (ICP) and cerebral blood flow (CBF) and from physiological and biochemical variables related to cerebral energy metabolism. Non-surgical therapies developed for treating increased ICP are based on knowledge regarding transport of water across the intact and injured blood-brain barrier (BBB) and the regulation of CBF. Brain volume is strictly controlled as the BBB permeability to crystalloids is very low restricting net transport of water across the capillary wall. Cerebral pressure autoregulation prevents changes in intracranial blood volume and intracapillary hydrostatic pressure at variations in arterial blood pressure. Information regarding cerebral oxidative metabolism is obtained from measurements of brain tissue oxygen tension (PbtO2) and biochemical data obtained from intracerebral microdialysis. As interstitial lactate/pyruvate (LP) ratio instantaneously reflects shifts in intracellular cytoplasmatic redox state, it is an important indicator of compromised cerebral oxidative metabolism. The combined information obtained from PbtO2, LP ratio, and the pattern of biochemical variables reveals whether impaired oxidative metabolism is due to insufficient perfusion (ischemia) or mitochondrial dysfunction. Intracerebral microdialysis and PbtO2 give information from a very small volume of tissue. Accordingly, clinical interpretation of the data must be based on information of the probe location in relation to focal brain damage. Attempts to evaluate global cerebral energy state from microdialysis of intraventricular fluid and from the LP ratio of the draining venous blood have recently been presented. To be of clinical relevance, the information

Traumatic brain injury (TBI) is a multidimensional and highly complex disease commonly resulting in widespread injury to axons, due to rapid inertial acceleration/deceleration forces transmitted to the brain during impact. Axonal injury leads to brain network dysfunction, significantly contributing to cognitive and functional impairments frequently observed in TBI survivors. Diffuse axonal injury (DAI) is a clinical entity suggested by impaired level of consciousness and coma on clinical examination and characterized by widespread injury to the hemispheric white matter tracts, the corpus callosum and the brain stem. The clinical course of DAI is commonly unpredictable and it remains a challenging entity with limited therapeutic options, to date. Although axonal integrity may be disrupted at impact, the majority of axonal pathology evolves over time, resulting from delayed activation of complex intracellular biochemical cascades. Activation of these secondary biochemical pathways may lead to axonal transection, named secondary axotomy, and be responsible for the clinical decline of DAI patients. Advances in the neurocritical care of TBI patients have been achieved by refinements in multimodality monitoring for prevention and early detection of secondary injury factors, which can be applied also to DAI. There is an emerging role for biomarkers in blood, cerebrospinal fluid, and interstitial fluid using microdialysis in the evaluation of axonal injury in TBI. These biomarker studies have assessed various axonal and neuroglial markers as well as inflammatory mediators, such as cytokines and chemokines. Moreover, modern neuroimaging can detect subtle or overt DAI/white matter changes in diffuse TBI patients across all injury severities using magnetic resonance spectroscopy, diffusion tensor imaging, and positron emission tomography. Importantly, serial neuroimaging studies provide evidence for evolving axonal injury. Since axonal injury may be a key risk factor for neuro