Publications by authors named "Celeste Dias"

25 Publications

  • Page 1 of 1

Impact of Phosphatemia Variability in Neurological Outcomes in Patients With Spontaneous Subarachnoid Hemorrhage.

Cureus 2021 Sep 24;13(9):e18257. Epub 2021 Sep 24.

Neurocritical Care Unit, Intensive Care Department, Hospital São João, Porto, PRT.

Introduction: Electrolyte disturbances, such as dysnatremia, hypokalemia, and hypomagnesemia, are frequently observed during acute spontaneous subarachnoid hemorrhage (sSAH). However, there are limited data concerning hypophosphatemia.

Objective: To analyze the frequency of phosphate (Pi) disturbances in sSAH patients and assess their influence on neurological outcomes compared with that in patients without sSAH.

Methods: We conducted a retrospective study of patients with sSAH admitted to a neurocritical care unit in two years. We also included nonneurocritical patients admitted to a general intensive care unit (ICU). Serum Pi levels and daily Pi repletion data were collected during the first 10 days after admission. The primary endpoint was neurologic outcome using the Glasgow Outcome Scale at six months (GOS-6M) and the Glasgow Coma Scale at ICU discharge (GCS-ICUd). The effect of phosphatemia variability on mortality and ICU length of stay (ICU-LOS) was also analyzed.

Results: Patients with sSAH had lower mean Pi level and median Pi dose repletion than that of nonneurocritical patients (3.1 ± 0.4 vs. 3.9 ± 1.3, p < 0.001). In the sSAH group, patients with hypophosphatemia had lower GCS-ICUd (12 ± 3.3 vs. 14 ± 2.4). Also, GOS-6M was lower in patients with hypophosphatemia but was not statistically significant (p = 0.09). By contrast, a higher mean Pi level in nonneurocritical patients was significantly associated with higher ICU mortality (4.8 ± 1.6 mg/dL vs. 3.6 ± 1.0 mg/dL, p = 0.003) and higher ICU-LOS (r = 0.231, p = 0.028). In the sSAH group, we found the opposite. In a multivariate analysis of the sSAH group, the increase in the Pi level was associated with higher GCS-ICUd (unstandardized coefficient in multiple linear regression [B] 1.79; 95% CI 0.43-3.15). The opposite was found in nonneurocritical patients. A Pi concentration higher than 2.5 mg/dL was associated with a better GCS-ICUd. We also found that creatinine, urea, chloride, need for Pi substitution, therapy intensity level, and pH were independent predictors of the mean Pi level during ICU stay in the sSAH group.

Conclusions: Patients with sSAH had lower mean Pi levels and required significantly higher daily Pi replacement compared with those of nonneurocritical patients. Since hypophosphatemia may be associated with poor neurological outcomes, patients with sSAH need cautious phosphate repletion.
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http://dx.doi.org/10.7759/cureus.18257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8544909PMC
September 2021

Erratum to 'The Effects of Temporary Clipping as an Expression of Circulatory Individuality: Online Measurement of Temporal Lobe Oxygen Levels During Surgery for Middle Cerebral Artery Aneurysms' [World Neurosurgery 152 (2021), e765-e775].

World Neurosurg 2021 Nov 7;155:230. Epub 2021 Sep 7.

Neurosurgery, Academic Hospital Centre, São João, Porto, Portugal; Department of Clinical Neurosciences, University of Porto, Porto, Portugal.

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http://dx.doi.org/10.1016/j.wneu.2021.08.124DOI Listing
November 2021

Low levels of TiO-nanoparticles interact antagonistically with Al and Pb alleviating their toxicity.

Plant Physiol Biochem 2021 Oct 21;167:1-10. Epub 2021 Jul 21.

LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, Campus Universitário de Santiago, 3810-193, Aveiro, Portugal. Electronic address:

The contamination and bioavailability of deleterious metals in arable soils significantly limits crop development and yield. Aiming at mitigating Pb- and Al-induced phytotoxicity, this work explores the use of P25 titanium dioxide nanoparticles (nTiO) in soil amendments. For that, Lactuca sativa L. plants were germinated and grown in the presence of 10 ppm Pb or 50 ppm Al, combined or not with 5 ppm nTiO. Growth parameters, as well as endpoints of the redox state [cell relative membrane permeability (RMP), thiobarbituric acid reactive substances content, total phenolic content and photosynthesis (sugars and pigments levels, chlorophyll a fluorescence and gas exchange), were evaluated. Concerning Al, nTiO treatment alleviated the impairments induced in germination rate, seedling length, water content, RMP, stomatal conductance (g), intercellular CO (C), and net CO assimilation rate (P). It increased anthocyanins contents and effective efficiency of photosystem II (Φ). In Pb-exposed plants, nTiO amendment mitigated the effects in RMP, P, g, and C. It also increased the pigment contents and the transpiration rate (E) comparatively to the control without nTiO. These results clearly highlight the high potential of low doses of nTiO in alleviating metal phytotoxicity, particularly the one of Pb. Additionally, further research should explore the use of these nanoparticles in agricultural soil amendments.
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http://dx.doi.org/10.1016/j.plaphy.2021.07.021DOI Listing
October 2021

Monitoring cerebrovascular reactivity in pediatric traumatic brain injury: comparison of three methods.

Childs Nerv Syst 2021 10 1;37(10):3057-3065. Epub 2021 Jul 1.

Brain Physics Laboratory, Division of Neurosurgery, Department of Clinical Neurosciences, Addenbrooke's Hospital, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.

Purpose: To study three different methods of monitoring cerebral autoregulation in children with severe traumatic brain injury.

Methods: Prospective cohort study of all children admitted to the pediatric intensive care unit at a university-affiliated hospital with severe TBI over a 4-year period to study three different methods of monitoring cerebral autoregulation: pressure-reactivity index (PRx), transcranial Doppler derived mean flow velocity index (Mx), and near-infrared spectroscopy derived cerebral oximetry index (COx).

Results: Twelve patients were included in the study, aged 5 months to 17 years old. An empirical regression analyzing dependence of PRx on cerebral perfusion pressure (CPP) displayed the classic U-shaped distribution, with low PRx values (< 0.3) reflecting intact auto-regulation, within the CPP range of 50-100 mmHg. The optimal CPP was 75-80 mmHg for PRx and COx. The correlation coefficients between the three indices were as follows: PRx vs Mx, r = 0.56; p < 0.0001; PRx vs COx, r = 0.16; p < 0.0001; and COx vs Mx, r = 0.15; p = 0.022. The mean PRx with a cutoff value of 0.3 predicted correctly long-term outcome (p = 0.015).

Conclusions: PRx seems to be the most robust index to access cerebrovascular reactivity in children with TBI and has promising prognostic value. Optimal CPP calculation is feasible with PRx and COx.
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http://dx.doi.org/10.1007/s00381-021-05263-zDOI Listing
October 2021

Effects of Temporary Clipping as an Expression of Circulatory Individuality: Online Measurement of Temporal Lobe Oxygen Levels During Surgery for Middle Cerebral Artery Aneurysms.

World Neurosurg 2021 08 25;152:e765-e775. Epub 2021 Jun 25.

Department of Neurosurgery, Academic Hospital Centre São João, Porto, Portugal; Department of Clinical Neurosciences, University of Porto, Porto, Portugal.

Objective: Despite its widespread use, much is left to understand about the repercussions of parent artery temporary clipping in neurosurgery. This study seeks a better comprehension of the subject by aiming at the online measurement of brain tissue oxygen pressure (PO) during such events.

Methods: This was a prospective observational study. Patients submitted to surgery for middle cerebral artery aneurysms (both ruptured and unruptured) were continuously monitored under Intensive Care Monitoring+ software, in order to obtain temporal (downstream) PO levels while temporary clips were applied. Separate PO curve events were identified, extracted, and processed. These were studied for assessing intraindividual and interindividual variability and the potential impact of repeated clipping and previous aneurysmal rupture.

Results: Eighty-six temporary clippings (from 20 patients) were recorded with a mean duration of 140.8 (41 - 238) seconds. Temporary arterial occlusion at the M1 segment of the middle cerebral artery produced specifically shaped trajectories, characterized by a preclipping PO level, rapid downward sigmoid-shaped curve, succession of progressively angled slopes, and lower plateau. The steepest slope of the curve correlated strongly with PO range (P < 0.001, r = 0.944). These features were highly reproducible only intraindividually and did not vary significantly with repeated clippings.

Conclusions: The effects of temporary arterial occlusion on temporal lobe oxygenation demonstrate a high degree of singularity, highlighting the potential benefits of assessing individual available collateral circulation intraoperatively. The "PO steepest slope" predicted the severity of PO decrease and was available within the first minute.
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http://dx.doi.org/10.1016/j.wneu.2021.06.082DOI Listing
August 2021

Monitoring of Cerebrovascular Reactivity in Intracerebral Hemorrhage and Its Relation with Survival.

Acta Neurochir Suppl 2021 ;131:187-190

Department of Intensive Care Medicine, Centro Hospitalar São João, Porto, Portugal.

Introduction: Neuromonitoring analysis for intracerebral hemorrhage (ICH) is still rare, especially regarding vascular reactivity patterns. Our goal was to analyze neuromonitoring data and 28-day mortality for ICH patients.

Methods: Neuromonitoring records were retrospectively reviewed from a cohort of ICH patients admitted to a neurocritical care unit between 2013 and 2016. Variables considered were intracranial pressure (ICP), cerebral perfusion pressure (CPP), optimal CPP, and pressure reactivity index (PRx), as well as ICP dose, PRx dose, and time percentage above critical value (T%abv). Information regarding demographics, surgical drainage, external ventricular drain placement, and 28-day mortality was recorded. Statistical analysis was performed using the t-test and Kaplan-Meier curves.

Results: Forty-six patients were analyzed, with a mean of 263 ± 173 h of signal records and a median length of stay in the intensive care unit of 22 (interquartile range of 13) days. The mean age was 62.6 ± 11.8 years old, and 24 (52%) of the patients were male. Patients who died within 28 day (37.0%) had significantly higher mean ICP, PRx, ICP dose, PRx dose, and T%abv. Although their mean ICP was under 20 mmHg, they presented PRx > 0.25, indicating impaired cerebrovascular reactivity (0.30 ± 0.26). Also, patients with PRx > 0.25 had a lower survival rate, with a proportion of 14% at 28 days, as opposed to 85% of those with PRx < 0.25 (p < 0.001).

Conclusion: The data suggest that autoregulation indexes are associated with 28-day mortality for ICH patients.
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http://dx.doi.org/10.1007/978-3-030-59436-7_37DOI Listing
June 2021

Comparison of Waveforms Between Noninvasive and Invasive Monitoring of Intracranial Pressure.

Acta Neurochir Suppl 2021 ;131:135-140

Faculty of Medicine, University of Porto, Al. Prof. Hernâni Monteiro, Porto, Portugal.

Intracranial pressure (ICP) is an important invasive monitoring parameter in management of patients with acute brain injury and compromised compliance. This study aimed to compare waveforms obtained from standard ICP monitoring and noninvasive ICP monitoring (nICP) methods.We analyzed continuous arterial blood pressure (ABP) waves, ICP (with standard monitoring), and nICP recorded simultaneously. All signal recordings were sliced into data chunks, each 1 min in duration, and from the mean pulse, we determined the time to peak (Tp) and the ratio between tidal and percussion waves (P2/P1). We also calculated the Isomap projection of the pulses into a bidimensional space-K1 and K2. The defined nICP and ICP parameters were compared using a unilateral Wilcoxon-Mann-Whitney test. The Pearson correlation coefficient and normalized mutual information were used to verify the association between parameters.In total, 1504 min of monitoring from ten patients were studied. Nine of the patients were male. The mean age of the patients was 58.4 ± 10.4 years, and they had an initial Glasgow Coma Scale of 9 ± 4, a mean Simplified Acute Physiology Score (SAPS II) of 45.6, and an intensive care unit stay of 44 ± 45 days. With the exception of Tp, all parameters showed a weak linear association but presented a strong nonlinear association.Mutual information analysis and a bigger sample size would be helpful to build more refined models and to improve understanding of the waveform relationships.
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http://dx.doi.org/10.1007/978-3-030-59436-7_28DOI Listing
June 2021

Brain Multimodal Monitoring in Severe Acute Brain Injury: Is It Relevant to Patient Outcome and Mortality?

Acta Neurochir Suppl 2021 ;131:83-86

Department of Intensive Care Medicine, Centro Hospitalar e Universitário São João, Porto, Portugal.

Introduction: Advanced multimodal monitoring (MMM) of the brain is recommended as a tool to manage severe acute brain injury in intensive care units (ICUs) and prevent secondary lesions. The aim of this study was to determine if MMM has implications for patient outcome and mortality.

Methods: We analyzed data on 389 patients admitted with a subarachnoid hemorrhage (SAH) or traumatic brain injury (TBI) to two general ICUs and one neurocritical care ICU (NCCU) between March 2014 and October 2016, and their subsequent outcomes.

Results: The study population consisted of 259 males and 130 females. Group 1, which comprised 69 patients with MMM admitted to the NCCU, was compared with group 2, which comprised patients managed without MMM. With the exceptions of the Simplified Acute Physiology Score (SAPS II) and Glasgow Coma Scale (GCS) scores, there were no differences between the two groups. Group 1 had significantly better outcomes at ICU discharge, at 28 days, and at 3 months, and also had a lower mortality rate (P < 0.05). When outcomes were adjusted for SAPS II scores, patients who had MMM had better outcomes (odds ratios 0.215 at ICU discharge, 0.234 at 28 days, 0.338 at 3 months, and 0.474 at 6 months) but no difference in mortality.

Conclusion: Use of MMM in patients with SAH or TBI is associated with better outcomes and should be considered in the management of these patients.
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http://dx.doi.org/10.1007/978-3-030-59436-7_18DOI Listing
June 2021

Non-ketotic hemichorea-hemiballismus presenting as generalised tonic-clonic convulsive state in uncontrolled diabetes.

BMJ Case Rep 2021 Feb 4;14(2). Epub 2021 Feb 4.

Neurocritical Care Unit, Centro Hospitalar Universitário de São João, Porto, Portugal.

We report the case of a 70-year-old diabetic woman who presented to the emergency department with multiple seizure episodes and coma, prompting the need for sedation and mechanical ventilation. She was transferred to our institution for neurosurgical evaluation as the initial CT scan identified hyperdense lesions in the left basal ganglia, interpreted as acute intracranial haemorrhage. On admission, laboratory tests were mostly normal except for blood glucose of 413 mg/dL. Medical records revealed a history of poorly controlled diabetes mellitus and non-adherence to therapy. After seizure control and lifting sedation, right-sided ataxia/involuntary movements were observed. Considering the patient's history and these findings, the CT scan was reviewed and the striatal region hyperdensities interpreted as lesions typical of non-ketotic hemichorea-hemiballismus. MRI was latter performed and confirmed the diagnosis, even though the unusual presentation. Levetiracetam initiation and glycaemic control optimisation led to great neurological improvement without seizure recurrence.
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http://dx.doi.org/10.1136/bcr-2020-240083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868197PMC
February 2021

Systemic inflammation status at admission affects the outcome of intracerebral hemorrhage by increasing perihematomal edema but not the hematoma growth.

Acta Neurol Belg 2021 Jun 7;121(3):649-659. Epub 2020 Jan 7.

Department of Clinical Neurosciences and Mental Health, Faculty of Medicine, University of Porto, Alameda Professor Hernâni Monteiro, 4200-319, Porto, Portugal.

Acute stress and inflammation responses are associated with worse outcomes in intracerebral hemorrhage (ICH) but the precise mechanisms involved are unclear. We evaluated the effect of neutrophil-to-lymphocyte ratio (NLR) in ICH outcome, with focus on hematoma expansion and early cerebral edema. In a retrospective study, we included all patients with primary ICH admitted to our center within 24-h from symptom onset from January 2014 to February 2015. We retrieved demographic and medical history data, Glasgow Coma Scale scores, blood cell counts, glucose, and C-reactive protein, and calculated NLR. We obtained hematoma volumes by computerized planimetry. Outcomes included independence at 90 days (modified Rankin scale 0-2), mortality at 30 days, significant hematoma expansion (> 33% or > 6 mL) and early cerebral edema causing significant midline shift (> 2.5 mm) at 24 h. We included 135 patients. NLR independently associated with independence at 90 days (adjusted odds ratio (aOR) 0.79, 95% CI 0.67-0.93, p = 0.006) significant cerebral edema (aOR 1.08, 95%CI 1.01-1.15, p = 0.016) but not hematoma expansion (aOR 0.99, 95%CI 0.94-1.04, p = 0.736). The severity of midline shift was positively correlated with NLR (adjusted beta = 0.08, 95% CI 0.05-0.11, p < 0.001). In ICH, an immediate and intense systemic inflammatory response reduces the likelihood of a better functional outcome at 90 days, which is more likely to be explained by perihematomal edema growth than due to a significant hematoma expansion. These findings could have implications in new treatment strategies and trial designs, which endpoints tend to target exclusively hematoma enlargement.
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http://dx.doi.org/10.1007/s13760-019-01269-2DOI Listing
June 2021

UV-B radiation modulates physiology and lipophilic metabolite profile in Olea europaea.

J Plant Physiol 2018 Mar 3;222:39-50. Epub 2018 Feb 3.

Department of Biology, LAQV/REQUIMTE, Faculty of Sciences, University of Porto, Rua do Campo Alegre, 4169-007 Porto, Portugal.

Ultraviolet-B (UV-B) radiation plays an important role in plant photomorphogenesis. Whilst the morpho-functional disorders induced by excessive UV irradiation are well-known, it remains unclear how this irradiation modulates the metabolome, and which metabolic shifts improve plants' tolerance to UV-B. In this study, we use an important Mediterranean crop, Olea europaea, to decipher the impacts of enhanced UV-B radiation on the physiological performance and lipophilic metabolite profile. Young olive plants (cv. 'Galega Vulgar') were exposed for five days to UV-B biologically effective doses of 6.5 kJ m d and 12.4 kJ m d. Cell cycle/ploidy, photosynthesis and oxidative stress, as well as GC-MS metabolites were assessed. Both UV-B treatments impaired net CO assimilation rate, transpiration rate, photosynthetic pigments, and RuBisCO activity, but 12.4 kJ m d also decreased the photochemical quenching (qP) and the effective efficiency of PSII (Φ). UV-B treatments promoted mono/triperpene pathways, while only 12.4 kJ m d increased fatty acids and alkanes, and decreased geranylgeranyl-diphosphate. The interplay between physiology and metabolomics suggests some innate ability of these plants to tolerate moderate UV-B doses (6.5 kJ m d). Also their tolerance to higher doses (12.4 kJ m d) relies on plants' metabolic adjustments, where the accumulation of specific compounds such as long-chain alkanes, palmitic acid, oleic acid and particularly oleamide (which is described for the first time in olive leaves) play an important protective role. This is the first study demonstrating photosynthetic changes and lipophilic metabolite adjustments in olive leaves under moderate and high UV-B doses.
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http://dx.doi.org/10.1016/j.jplph.2018.01.004DOI Listing
March 2018

Monitoring of Optimal Cerebral Perfusion Pressure in Traumatic Brain Injured Patients Using a Multi-Window Weighting Algorithm.

J Neurotrauma 2017 11 2;34(22):3081-3088. Epub 2017 Aug 2.

1 Brain Physics Laboratory, Division of Neurosurgery, Department of Clinical Neurosciences, Addenbrooke's Hospital, University of Cambridge , Cambridge, United Kingdom .

Methods to identify an autoregulation guided "optimal" cerebral perfusion pressure (CPPopt) for traumatic brain injury patients (TBI) have been reported through several studies. An important drawback of existing methodology is that CPPopt can be calculated only in ∼50-60% of the monitoring time. In this study, we hypothesized that the CPPopt yield and the continuity can be improved significantly through application of a multi-window and weighting calculation algorithm, without adversely affecting preservation of its prognostic value. Data of 526 severe TBI patients admitted between 2003 and 2015 were studied. The multi-window CPPopt calculation was based on automated curve fitting in pressure reactivity index (PRx)-CPP plots using data from 36 increasing length time windows (2-8 h). The resulting matrix of CPPopts was then averaged in a weighted manner. The yield, continuity, and stability of CPPopt were studied. The difference between patients' actual CPP and CPPopt (ΔCPP) was calculated and the association with outcome was analyzed. Overall, the multi-window method demonstrated more continuous and stable presentation of CPPopt in this cohort. The new method resulted in a mean (±SE) CPPopt yield of 94% ± 2.1%, as opposed to the previous single-window-based CPPopt yield of 51% ± 0.94%. The stability of CPPopt across the whole monitoring period was significantly improved by using the new algorithm (p < 0.001). The relationship between ΔCPP according to the multi-window algorithm and outcome was similar to that for CPPopt calculated on the basis of a single window. In conclusion, this study validates the use of a new multi-window and weighting algorithm for significant improvement of CPPopt yield in TBI patients. This methodological improvement is essential for its clinical application in future CPPopt trials.
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http://dx.doi.org/10.1089/neu.2017.5003DOI Listing
November 2017

Plateau Waves of Intracranial Pressure and Multimodal Brain Monitoring.

Acta Neurochir Suppl 2016 ;122:143-6

Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.

The aim of this study was to describe multimodal brain monitoring characteristics during plateau waves of intracranial pressure (ICP) in patients with head injury, using ICM+ software for continuous recording. Plateau waves consist of an abrupt elevation of ICP above 40 mmHg for 5-20 min. This is a prospective observational study of patients with head injury who were admitted to a neurocritical care unit and who developed plateau waves. We analyzed 59 plateau waves that occurred in 8 of 18 patients (44 %). At the top of plateau waves arterial blood pressure remained almost constant, but cerebral perfusion pressure, cerebral blood flow, brain tissue oxygenation, and cerebral oximetry decreased. After plateau waves, patients with a previously better autoregulation status developed hyperemia, demonstrated by an increase in cerebral blood flow and brain oxygenation. Pressure and oxygen cerebrovascular reactivity indexes (pressure reactivity index and ORxshort) increased significantly during the plateau wave as a sign of disruption of autoregulation. Bedside multimodal brain monitoring is important to characterize increases in ICP and give differential diagnoses of plateau waves, as management of this phenomenon differs from that of regular ICP.
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http://dx.doi.org/10.1007/978-3-319-22533-3_29DOI Listing
July 2017

Validation of a New Minimally Invasive Intracranial Pressure Monitoring Method by Direct Comparison with an Invasive Technique.

Acta Neurochir Suppl 2016 ;122:97-100

University of São Paulo, Sao Paulo, Brazil.

In this chapter we present in vivo experiments with a new minimally invasive method of monitoring intracranial pressure (ICP). Strain gauge deformation sensors are externally glued onto the exposed skull. The signal from these sensors is amplified, filtered, and sent to a computer with appropriate software for analysis and data storage. Saline infusions into the spinal channel of rats were performed to produce ICP changes, and minimally invasive ICP and direct Codman intraparenchymal ICP were simultaneously acquired in six animals. The similarity between the invasive and minimally invasive methods in response to ICP increase was assessed using Pearson's correlation coefficient. It demonstrated good agreement between the two measures < r > = 0.8 ± 0.2, with a range of 0.31-0.99.
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http://dx.doi.org/10.1007/978-3-319-22533-3_19DOI Listing
July 2017

Validation of a New Noninvasive Intracranial Pressure Monitoring Method by Direct Comparison with an Invasive Technique.

Acta Neurochir Suppl 2016 ;122:93-6

University of São Paulo, São Paulo, Brazil.

The search for a completely noninvasive intracranial pressure (ICPni) monitoring technique capable of real-time digitalized monitoring is the Holy Grail of brain research. If available, it may facilitate many fundamental questions within the range of ample applications in neurosurgery, neurosciences and translational medicine, from pharmaceutical clinical trials, exercise physiology, and space applications. In this work we compare invasive measurements with noninvasive measurements obtained using the proposed new noninvasive method. Saline was infused into the spinal channel of seven rats to produce ICP changes and the simultaneous acquisition of both methods was performed. The similarity in the invasive and noninvasive methods of ICP monitoring was calculated using Pearson's correlation coefficients (r). Good agreement between measures < r > = 0.8 ± 0.2 with a range 0.28-0.96 was shown.
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http://dx.doi.org/10.1007/978-3-319-22533-3_18DOI Listing
July 2017

Clinical and Physiological Events That Contribute to the Success Rate of Finding "Optimal" Cerebral Perfusion Pressure in Severe Brain Trauma Patients.

Crit Care Med 2015 Sep;43(9):1952-63

1Division of Neurosurgery, Department of Clinical Neurosciences, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom. 2Department of Neurosurgery, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands. 3Department of Critical Care, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands. 4Department of Intensive Care, Neurocritical Care Unit, Hospital Sao Joao, Porto, Portugal.

Objective: Recently, a concept of an individually targeted level of cerebral perfusion pressure that aims to restore impaired cerebral vasoreactivity has been advocated after traumatic brain injury. The relationship between cerebral perfusion pressure and pressure reactivity index normally is supposed to have a U-shape with its minimum interpreted as the value of "optimal" cerebral perfusion pressure. The aim of this study is to investigate the relation between the absence of the optimal cerebral perfusion pressure curve and physiological variables, clinical factors, and interventions.

Design: Retrospective analysis of prospectively collected data.

Setting: Neurocritical care units in two university centers.

Patients: Between May 2012 and December 2013, a total of 48 traumatic brain injury patients were studied with real-time annotation of predefined clinical events.

Interventions: None.

Measurements And Main Results: All patients had continuous monitoring of arterial blood pressure, intracranial pressure, and cerebral perfusion pressure, with real-time calculations of pressure reactivity index and optimal cerebral perfusion pressure using ICM+ software (Cambridge Enterprise, University of Cambridge, Cambridge, UK). Selected clinical events were inserted on a daily basis, including changes in physiological variables, sedativeanalgesic drugs, vasoactive drugs, and medical/surgical therapies for intracranial hypertension. The collected data were divided into 4-hour periods, with the primary outcome being absence of the optimal cerebral perfusion pressure curve. For every period, mean values (± SDs) of arterial blood pressure, intracranial pressure, pressure reactivity index, and other physiological variables were calculated; clinical events were organized using predefined scales. In 28% of all 1,561 periods, an optimal cerebral perfusion pressure curve was absent. A generalized linear mixed model with binary logistic regression was fitted. Absence of slow arterial blood pressure waves (odds ratio, 2.7; p < 0.001), higher pressure reactivity index values (odds ratio, 2.9; p < 0.001), lower amount of sedative-analgesic drugs (odds ratio, 1.9; p = 0.03), higher vasoactive medication dose (odds ratio, 3.2; p = 0.02), no administration of maintenance neuromuscular blockers (odds ratio, 1.7; p < 0.01), and following decompressive craniectomy (odds ratio, 1.8; p < 0.01) were independently associated with optimal cerebral perfusion pressure curve absence.

Conclusions: This study identified six factors that were independently associated with absence of optimal cerebral perfusion pressure curves.
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http://dx.doi.org/10.1097/CCM.0000000000001165DOI Listing
September 2015

Optimal Cerebral Perfusion Pressure Management at Bedside: A Single-Center Pilot Study.

Neurocrit Care 2015 Aug;23(1):92-102

Neurocritical Care Unit, Intensive Care Department, Hospital Sao Joao, Porto, Portugal,

Background: Guidelines recommend cerebral perfusion pressure (CPP) values of 50-70 mmHg and intracranial pressure lower than 20 mmHg for the management of acute traumatic brain injury (TBI). However, adequate individual targets are still poorly addressed, since patients have different perfusion thresholds. Bedside assessment of cerebral autoregulation may help to optimize individual CPP-guided treatment.

Objective: To assess staff compliance and outcome impact of a new method of autoregulation-guided treatment (CPPopt) based on continuous evaluation of cerebrovascular reactivity (PRx).

Methods: Prospective pilot study of severe TBI adult patients managed with continuous multimodal brain monitoring in a single Neurocritical Care Unit (NCCU). Every minute CPPopt was automatically estimated, based on the previous 4-h window, as the CPP with the lowest PRx indicating the best cerebrovascular pressure reactivity. Patients were managed with CPPopt targets whenever possible and otherwise CPP was managed following general/international guidelines. In addition, other offline CPPopt estimates were calculated using cerebral oximetry (COx-CPPopt), brain tissue oxygenation (ORxs-CPPopt), and cerebral blood flow (CBFx-CPPopt).

Results: Eighteen patients with a total multimodal brain monitoring time of 5,520 h were enrolled. During the total monitoring period, 11 patients (61 %) had a CPPopt U-shaped curve, 5 patients (28 %) had either ascending or descending curves, and only 2 patients (11 %) had no fitted curve. Real CPP correlated significantly with calculated CPPopt (r = 0.83, p < 0.0001). Preserved autoregulation was associated with greater Glasgow coma score on admission (p = 0.01) and better outcome (p = 0.01). We demonstrated that patients with the larger discrepancy (>10 mm Hg) between real CPP and CPPopt more likely have had adverse outcome (p = 0.04). Comparison between CPPopt and the other estimates revealed similar limits of precision. The lowest bias (-0.1 mmHg) was obtained with COx-CPPopt (NIRS).

Conclusion: Targeted individual CPP management at the bedside using cerebrovascular pressure reactivity seems feasible. Large deviation from CPPopt seems to be associated with adverse outcome. The COx-CPPopt methodology using non-invasive CO (NIRS) warrants further evaluation.
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http://dx.doi.org/10.1007/s12028-014-0103-8DOI Listing
August 2015

Kidney-brain link in traumatic brain injury patients? A preliminary report.

Neurocrit Care 2015 Apr;22(2):192-201

Intensive Care Department, Neurocritical Care Unit, Hospital Sao Joao, Porto, Portugal,

Background: Kidney hyperfiltration with augmented renal clearance is frequently observed in patients with traumatic brain injury. The aim of this study is to report preliminary findings about the relationship between brain autoregulation impairment, estimated kidney glomerular filtration rate and outcome in critically ill patients after severe traumatic brain injury.

Methods: Data collected from a cohort of 18 consecutive patients with severe traumatic brain injury managed with ICP monitoring in a Neurocritical Care Unit, were retrospectively analyzed. Early morning blood tests were performed for routine chemistry assessments and we analyzed creatinine and estimated creatinine clearance, osmolarity, and sodium. Daily norepinephrine dose, protein intake, and water balance were documented. Time average of brain monitoring data (intracranial pressure, cerebral perfusion pressure, and cerebrovascular reactivity pressure index--PRx) were calculated for 6 h before blood sample tests. Patient outcome was evaluated using Glasgow outcome scale at 6-month follow-up, considering nonfatal outcome if GOS ≥ 3 and fatal outcome if GOS < 3. Multiple linear regression models were used to study the crude and adjusted effects of the above variables on PRx throughout time.

Results: A total of 199 complete daily observations from 18 adult consecutive multiple trauma patients with severe traumatic brain injury were analyzed. At hospital admission, the median post-resuscitation Glasgow coma score was 6 (range 3-12), mean SAPSII score was 44.65 with predicted mortality of 36 %. Hospital mortality rate was 27 % and median GOS at 6 month after discharge was 3. Creatinine clearance (CrCl) was found to have a negative correlation with PRx (Pearson correlation--0.82), with statistically significant crude (p < 0.001) and adjusted (p = 0.001) effects. For each increase of 10 ml/min in CrCl (estimated either by the Cockcroft-Gault or by Modification of Diet in Renal Disease Study equations) a mean decrease in PRx of approximately 0.01 was expected. Amongst possible confounders only norepinephrine was shown to have a significant effect. Mean PRx value for outcome fatal status was greater than mean PRx for nonfatal status (p < 0.05), regardless of the model used for the CrCl estimation.

Conclusions: Better cerebral autoregulation evaluated with cerebrovascular PRx is significantly correlated with augmented renal clearance in TBI patients and associates with better outcome.
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http://dx.doi.org/10.1007/s12028-014-0045-1DOI Listing
April 2015

Increased blood glucose is related to disturbed cerebrovascular pressure reactivity after traumatic brain injury.

Neurocrit Care 2015 Feb;22(1):20-5

Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge Biomedical Campus, Box 167, Cambridge, CB2 0QQ, UK,

Background: Increased blood glucose and impaired pressure reactivity (PRx) after traumatic brain injury (TBI) are both known to correlate with unfavorable patient outcome. However, the relationship between these two variables is unknown.

Methods: To test the hypothesis that increased blood glucose leads to increased PRx, we retrospectively analyzed data from 86 traumatic brain injured patients admitted to the Neurocritical Care Unit. Data analyzed included arterial glucose concentration, intracranial pressure (ICP), cerebral perfusion pressure (CPP) and end-tidal CO2. PRx was calculated as the moving correlation coefficient between averaged (10 seconds) arterial blood pressure and ICP. One arterial glucose concentration and one time-aligned PRx value were obtained for each patient, during each day until the fifth day after ictus.

Results: Mean arterial glucose concentrations during the first 5 days since ictus were positively correlated with mean PRx (Pearson correlation coefficient = 0.25, p = 0.02). The correlation was strongest on the first day after injury (Pearson correlation coefficient = 0.47, p = 0.008).

Conclusion: Our preliminary findings indicate that increased blood glucose may impair cerebrovascular reactivity, potentially contributing to a mechanistic link between increased blood glucose and poorer outcome after TBI.
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http://dx.doi.org/10.1007/s12028-014-0042-4DOI Listing
February 2015

Traumatic brain injury in Portugal: trends in hospital admissions from 2000 to 2010.

Acta Med Port 2014 May-Jun;27(3):349-56. Epub 2014 Jun 30.

Neurosurgery Department. Hospital São João. University of Porto. Porto. Portugal.

Introduction: Traumatic brain injury has a considerable socio-economic impact, being a major cause of morbi-mortality, often with permanent disability. We sought to characterize health resource utilization of adult traumatic brain injury patients in Portugal between 2000 and 2010.

Material And Methods: Retrospective study of medical records of adult patients with ICD9 diagnostic code of traumatic brain injury included in the National Diagnosis Related Groups Database from 2000-2010. Descriptive statistical analysis was performed and trends during the decade were evaluated.

Results: We analysed 72 865 admissions to 111 hospitals, 64.1% males, mean age 57.9 ± 21.8 years (18-107). We found a decrease in number of traumatic brain injury in younger patients and an increase in older ones. The number of traffic accidents decreased and the number of falls increased. There was an increase of moderate to severe traumatic brain injury admissions: 47.2% in 2000 / 80% in 2010. Patients admitted in Intensive Care have nearly doubled (15.8% vs 29.5%) as well as the number submitted to neurosurgical procedures (8.2% vs 15.2%). Total mortality increased from 7.1% to 10.6%.

Discussion: The decrease of traumatic brain injury may be associated with the trauma prevention campaigns, road network improvement and health politics. The increase in mortality may be related to better pre-hospital care, enabling more severe cases to arrive in hospital alive, and although treated more frequently in Intensive Care and requiring more neurosurgical procedures, they end up having higher mortality. Also this may be due to an increase in patients' age and worse pre-morbid status.

Conclusion: Traumatic brain injury in Portugal is changing. Although hospital admissions due to global traumatic brain injury have decreased, mortality rate has increased.
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http://dx.doi.org/10.20344/amp.4892DOI Listing
March 2016

Post-traumatic multimodal brain monitoring: response to hypertonic saline.

J Neurotrauma 2014 Nov 11;31(22):1872-80. Epub 2014 Sep 11.

1 Department of Intensive Care, University Hospital Sao Joao , Porto, Portugal .

Emerging evidence suggests that hypertonic saline (HTS) is efficient in decreasing intracranial pressure (ICP). However there is no consensus about its interaction with brain hemodynamics and oxygenation. In this study, we investigated brain response to HTS bolus with multimodal monitoring after severe traumatic brain injury (TBI). We included 18 consecutive TBI patients during 10 days after neurocritical care unit admission. Continuous brain monitoring applied included ICP, tissue oxygenation (PtO2) and cerebral blood flow (CBF). Cerebral perfusion pressure (CPP), cerebrovascular resistance (CVR), and reactivity indices related to pressure (PRx) and flow (CBFx) were calculated. ICM+software was used to collect and analyze monitoring data. Eleven of 18 (61%) patients developed 99 episodes of intracranial hypertension (IHT) greater than 20 mm Hg that were managed with 20% HTS bolus. Analysis over time was performed with linear mixed-effects regression modelling. After HTS bolus, ICP and CPP improved over time (p<0.001) following a quadratic model. From baseline to 120 min, ICP had a mean decrease of 6.2 mm Hg and CPP a mean increase of 3.1 mmHg. Mean increase in CBF was 7.8 mL/min/100 g (p<0.001) and mean decrease in CVR reached 0.4 mm Hg*min*100 g/mL (p=0.01). Both changes preceded pressures improvement. PtO2 exhibited a marginal increase and no significant models for time behaviour could be fitted. PRx and CBFx were best described by a linear decreasing model showing autoregulation recover after HTS (p=0.01 and p=0.04 respectively). During evaluation, CO2 remained constant and sodium level did not exhibit significant variation. In conclusion, management of IHT with 20% HTS significantly improves cerebral hemodynamics and cerebrovascular reactivity with recovery of CBF appearing before rise in CPP and decrease in ICP. In spite of cerebral hemodynamic improvement, no significant changes in brain oxygenation were identified.
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http://dx.doi.org/10.1089/neu.2014.3376DOI Listing
November 2014

Continuous time-domain monitoring of cerebral autoregulation in neurocritical care.

Med Eng Phys 2014 May 1;36(5):638-45. Epub 2014 Apr 1.

Academic Neurosurgical Unit, University of Cambridge Department of Clinical Neurosciences, Cambridge, United Kingdom.

Integration of various brain signals can be used to determine cerebral autoregulation in neurocritical care patients to guide clinical management and to predict outcome. In this review, we will discuss current methodology of multimodal brain monitoring focusing on secondary 'reactivity indices' derived from various brain signals which are based on a 'moving correlation coefficient'. This algorithm was developed in order to analyze in a time dependent manner the degree of correlation between two factors within a time series where the number of paired observations is large. Of the various primary neuromonitoring sources which can be used to calculate reactivity indices, we will focus in this review on indices based on transcranial Doppler (TCD), intracranial pressure (ICP), brain tissue oxygenation (PbtO2) and near infrared spectroscopy (NIRS). Furthermore, we will demonstrate how reactivity indices can show transient changes of cerebral autoregulation and can be used to optimize management of arterial blood pressure (ABP) and cerebral perfusion pressure (CPP).
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http://dx.doi.org/10.1016/j.medengphy.2014.03.002DOI Listing
May 2014

Pressures, flow, and brain oxygenation during plateau waves of intracranial pressure.

Neurocrit Care 2014 Aug;21(1):124-32

Intensive Care Department, Neurocritical Care Unit, Hospital Sao Joao, Porto, Portugal,

Background: Plateau waves are common in traumatic brain injury. They constitute abrupt increases of intracranial pressure (ICP) above 40 mmHg associated with a decrease in cerebral perfusion pressure (CPP). The aim of this study was to describe plateau waves characteristics with multimodal brain monitoring in head injured patients admitted in neurocritical care.

Methods: Prospective observational study in 18 multiple trauma patients with head injury admitted to Neurocritical Care Unit of Hospital Sao Joao in Porto. Multimodal systemic and brain monitoring of primary variables [heart rate, arterial blood pressure, ICP, CPP, pulse amplitude, end tidal CO₂, brain temperature, brain tissue oxygenation pressure, cerebral oximetry (CO) with transcutaneous near-infrared spectroscopy and cerebral blood flow (CBF)] and secondary variables related to cerebral compensatory reserve and cerebrovascular reactivity were supported by dedicated software ICM+ ( www.neurosurg.cam.ac.uk/icmplus) . The compiled data were analyzed in patients who developed plateau waves.

Results: In this study we identified 59 plateau waves that occurred in 44% of the patients (8/18). During plateau waves CBF, cerebrovascular resistance, CO, and brain tissue oxygenation decreased. The duration and magnitude of plateau waves were greater in patients with working cerebrovascular reactivity. After the end of plateau wave, a hyperemic response was recorded in 64% of cases with increase in CBF and brain oxygenation. The magnitude of hyperemia was associated with better autoregulation status and low oxygenation levels at baseline.

Conclusions: Multimodal brain monitoring facilitates identification and understanding of intrinsic vascular brain phenomenon, such as plateau waves, and may help the adequate management of acute head injury at bed side.
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http://dx.doi.org/10.1007/s12028-013-9918-yDOI Listing
August 2014

Portable miniaturized extracorporeal membrane oxygenation systems for H1N1-related severe acute respiratory distress syndrome: a case series.

J Crit Care 2012 Oct 3;27(5):454-63. Epub 2012 Mar 3.

Department of Intensive Care Medicine, Hospital de S.João, Porto, Portugal.

Background: Technological advances improved the practice of "modern" extracorporeal membrane oxygenation (ECMO). In the present report, we describe the experience of a referral ECMO center using portable miniaturized ECMO systems for H1N1-related severe acute respiratory distress syndrome (ARDS).

Methods: An observational study of all patients with H1N1-associated ARDS treated with ECMO in Hospital S. João (Porto, Portugal) between November 2009 and April 2011 was performed. Extracorporeal membrane oxygenation support was established using either ELS or Cardiohelp systems (Maquet-Cardiopulmonary-AG, Hirrlingen, Germany).

Results: Ten adult patients with severe ARDS secondary to H1N1 infection (Pao(2)/fraction of inspired oxygen, 69 mm Hg [56-84]; Murray score, 3.5 [3.5-3.8]) were included, and 60% survived to hospital discharge. Five patients were uneventfully transferred on ECMO from referring hospitals to our center by ambulance. Six patients were treated during the first postpandemic influenza season. All patients were treated with oseltamivir, and 1 received in addition zanamivir. Four patients received corticosteroids. Nosocomial infection was the most common complication (40%). Of the 4 deaths, 2 were caused by hemorrhagic shock; 1, by irreversible multiple organ failure; and 1, by refractory septic shock.

Conclusion: In our experience, ECMO support was a valuable therapeutic option for H1N1-related severe ARDS. The use of portable miniaturized systems allowed urgent rescue of patients from referring hospitals and safe interhospital and intrahospital transport during ECMO support.
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http://dx.doi.org/10.1016/j.jcrc.2012.01.008DOI Listing
October 2012

Monitoring of brain oxygenation in surgery of ruptured middle cerebral artery aneurysms.

Surg Neurol Int 2011 28;2:70. Epub 2011 May 28.

Department of Neurosurgery, Hospital S. João, Porto, Portugal.

Background: The occurrence of brain ischemic lesions, due to temporary arterial occlusion or incorrect placement of the definitive clip, is a major complication of aneurysm surgery. Temporary clipping is a current technique during surgery and there is no reliable method of predicting the possibility of ischemia due to extended regional circulatory interruption. Even with careful inspection, misplacement of the definitive clip can be difficult to detect. Brain tissue oxygen concentration (PtiO(2)) was monitored during surgery of middle cerebral artery (MCA) aneurysm presenting with subarachnoid hemorrhage (SAH), for detection of changes in brain oxygenation due to reduced blood flow, as a predictor of ischemic events, during temporary clipping and after definitive clipping.

Methods: PtiO(2) was monitored during surgery of 13 patients harboring MCA aneurysms presenting with SAH, using a polarographic microcatheter (Licox, GMS, Kiel, Germany) placed in the territory of MCA.

Results: A decrease in PtiO(2) values was verified in every period of temporary clipping. Brain infarction occurred in 2 patients; in both cases, there was a decrease in PtiO(2) greater than 80% from basal value, a minimum value of less than 2 mmHg persisting for 2 or more minutes during temporary clipping, and an incomplete recovery of PtiO(2) after definitive clipping. In 2 patients, incomplete recovery of values after definitive clipping led to verification of inappropriate placement and repositioning of the clip.

Conclusion: The results suggest that intraoperative monitoring of PtiO(2) may be a useful method of detection of changes in brain tissue oxygenation during MCA aneurysm surgery. Postoperative infarction in the territory of MCA developed in cases with an abrupt decrease of PtiO(2) and a very low and persistent minimum value, during temporary clipping, and an incomplete recovery after definitive clipping. Verification of clip position should be considered when there is an incomplete recovery or a persistent fall in PtiO(2) after definitive clipping.
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http://dx.doi.org/10.4103/2152-7806.81732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3115273PMC
July 2011
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