Combined depth and scalp electroencephalographic monitoring in acute brain injury: Yield and prognostic value.

BACKGROUND AND PURPOSE: Depth electroencephalography (dEEG) is an emerging neuromonitoring technology in acute brain injury (ABI). We aimed to explore the concordances between electrophysiological activities on dEEG and on scalp EEG (scEEG) in ABI patients. METHODS: Consecutive ABI patients who received dEEG monitoring between 2018 and 2022 were included. Background, sporadic epileptiform discharges, rhythmic and periodic patterns (RPPs), electrographic seizures, brief potentially ictal rhythmic discharges, ictal-interictal continuum (IIC) patterns, and hourly RPP burden on dEEG and scEEG were compared. RESULTS: Sixty-one ABI patients with a median dEEG monitoring duration of 114 h were included. dEEG significantly showed less continuous background (75% vs. 90%, p = 0.03), higher background amplitude (p < 0.001), more frequent rhythmic spike-and-waves (16% vs. 3%, p = 0.03), more IIC patterns (39% vs. 21%, p = 0.03), and greater hourly RPP burden (2430 vs. 1090 s/h, p = 0.01), when compared to scEEG. Among five patients with seizures on scEEG, one patient had concomitant seizures on dEEG, one had periodic discharges (not concomitant) on dEEG, and three had no RPPs on dEEG. Features and temporal occurrence of electrophysiological activities observed on dEEG and scEEG are not strongly associated. Patients with seizures and IIC patterns on dEEG seemed to have a higher rate of poor outcomes at discharge than patients without these patterns on dEEG (42% vs. 25%, p = 0.37). CONCLUSIONS: dEEG can detect abnormal electrophysiological activities that may not be seen on scEEG and can be used as a complement in the neuromonitoring of ABI patients.

The impact of perfusion computed tomography on the diagnosis and outcome of delayed cerebral ischemia after subarachnoid hemorrhage.

BACKGROUND: Delayed cerebral ischemia (DCI) is a preventable cause of poor neurological outcome in aneurysmal subarachnoid hemorrhage (aSAH). Advances in radiological methods, such as cerebral perfusion computed tomography (CTP), could help diagnose DCI earlier and potentially improve outcomes in aSAH. The objective of this study was to assess whether the use of CTP to diagnose DCI early could reduce the risk of infarction related to DCI. METHODS: Retrospective cohort study of patients in the intensive care unit of Erasme Hospital (Brussels, Belgium) between 2004 and 2021 with aSAH who developed DCI. Patients were classified as: "group 1" - DCI diagnosed based on clinical deterioration or "group 2" - DCI diagnosed using CTP. The primary outcome was the development of infarction unrelated to the initial bleeding or surgery. RESULTS: 211 aSAH patients were diagnosed with DCI during the study period: 139 (66%) in group 1 and 72 (34%) in group 2. In group 1, 109 (78%) patients developed a cerebral infarction, compared to 45 (63%) in group 2 (p = 0.02). The adjusted cumulative incidence of DCI over time was lower in group 2 than in group 1 [hazard ratio 0.65 (95% CI 0.48-0.94); p = 0.02]. The use of CTP to diagnose DCI was not independently associated with mortality or neurological outcome. CONCLUSIONS: The use of CTP to diagnose DCI might help reduce the risk of developing cerebral infarction after aSAH, although the impact of such an approach on patient outcomes needs to be further demonstrated.

Brain Oxygenation Response to Hypercapnia in Patients with Acute Brain Injury.

BACKGROUND: Cerebral hypoxia is a frequent cause of secondary brain damage in patients with acute brain injury. Although hypercapnia can increase intracranial pressure, it may have beneficial effects on tissue oxygenation. We aimed to assess the effects of hypercapnia on brain tissue oxygenation (PbtO2). METHODS: This single-center retrospective study (November 2014 to June 2022) included all patients admitted to the intensive care unit after acute brain injury who required multimodal monitoring, including PbtO2 monitoring, and who underwent induced moderate hypoventilation and hypercapnia according to the decision of the treating physician. Patients with imminent brain death were excluded. Responders to hypercapnia were defined as those with an increase of at least 20% in PbtO2 values when compared to their baseline levels. RESULTS: On a total of 163 eligible patients, we identified 23 (14%) patients who underwent moderate hypoventilation (arterial partial pressure of carbon dioxide [PaCO2] from 44 [42-45] to 50 [49-53] mm Hg; p < 0.001) during the study period at a median of 6 (4-10) days following intensive care unit admission; six patients had traumatic brain injury, and 17 had subarachnoid hemorrhage. A significant overall increase in median PbtO2 values from baseline (21 [19-26] to 24 [22-26] mm Hg; p = 0.02) was observed. Eight (35%) patients were considered as responders, with a median increase of 7 (from 4 to 11) mm Hg of PbtO2, whereas nonresponders showed no changes (from - 1 to 2 mm Hg of PbtO2). Because of the small sample size, no variable independently associated with PbtO2 response was identified. No correlation between changes in PaCO2 and in PbtO2 was observed. CONCLUSIONS: In this study, a heterogeneous response of PbtO2 to induced hypercapnia was observed but without any deleterious elevations of intracranial pressure.

Cardiac Injury After Traumatic Brain Injury: Clinical Consequences and Management.

Traumatic brain injury (TBI) is a significant public health issue because of its increasing incidence and the substantial short-term and long-term burden it imposes. This burden includes high mortality rates, morbidity, and a significant impact on productivity and quality of life for survivors. During the management of TBI, extracranial complications commonly arise during the patient's stay in the intensive care unit. These complications can have an impact on both mortality and the neurological outcome of patients with TBI. Among these extracranial complications, cardiac injury is a relatively frequent occurrence, affecting approximately 25-35% of patients with TBI. The pathophysiology underlying cardiac injury in TBI involves the intricate interplay between the brain and the heart. Acute brain injury triggers a systemic inflammatory response and a surge of catecholamines, leading to the release of neurotransmitters and cytokines. These substances have detrimental effects on the brain and peripheral organs, creating a vicious cycle that exacerbates brain damage and cellular dysfunction. The most common manifestation of cardiac injury in TBI is corrected QT (QTc) prolongation and supraventricular arrhythmias, with a prevalence up to 5 to 10 times higher than in the general adult population. Other forms of cardiac injury, such as regional wall motion alteration, troponin elevation, myocardial stunning, or Takotsubo cardiomyopathy, have also been described. In this context, the use of ß-blockers has shown potential benefits by intervening in this maladaptive process. ß-blockers can limit the pathological effects on cardiac rhythm, blood circulation, and cerebral metabolism. They may also mitigate metabolic acidosis and potentially contribute to improved cerebral perfusion. However, further clinical studies are needed to elucidate the role of new therapeutic strategies in limiting cardiac dysfunction in patients with severe TBI.

Pulsed Hyperoxia Acts on Plasmatic Advanced Glycation End Products and Advanced Oxidation Protein Products and Modulates Mitochondrial Biogenesis in Human Peripheral Blood Mononuclear Cells: A Pilot Study on the "Normobaric Oxygen Paradox".

The "normobaric oxygen paradox" (NOP) describes the response to the return to normoxia after a hyperoxic event, sensed by tissues as an oxygen shortage, up-regulating redox-sensitive transcription factors. We have previously characterized the time trend of oxygen-sensitive transcription factors in human PBMCs, in which the return to normoxia after 30% oxygen is sensed as a hypoxic trigger, characterized by hypoxia-induced factor (HIF-1) activation. On the contrary, 100% and 140% oxygen induce a shift toward an oxidative stress response, characterized by NRF2 and NF-kB activation in the first 24 h post exposure. Herein, we investigate whether this paradigm triggers Advanced Glycation End products (AGEs) and Advanced Oxidation Protein Products (AOPPs) as circulating biomarkers of oxidative stress. Secondly, we studied if mitochondrial biogenesis was involved to link the cellular response to oxidative stress in human PBMCs. Our results show that AGEs and AOPPs increase in a different manner according to oxygen dose. Mitochondrial levels of peroxiredoxin (PRX3) supported the cellular response to oxidative stress and increased at 24 h after mild hyperoxia, MH (30% O2), and high hyperoxia, HH (100% O2), while during very high hyperoxia, VHH (140% O2), the activation was significantly high only at 3 h after oxygen exposure. Mitochondrial biogenesis was activated through nuclear translocation of PGC-1α in all the experimental conditions. However, the consequent release of nuclear Mitochondrial Transcription Factor A (TFAM) was observed only after MH exposure. Conversely, HH and VHH are associated with a progressive loss of NOP response in the ability to induce TFAM expression despite a nuclear translocation of PGC-1α also occurring in these conditions. This study confirms that pulsed high oxygen treatment elicits specific cellular responses, according to its partial pressure and time of administration, and further emphasizes the importance of targeting the use of oxygen to activate specific effects on the whole organism.

Oxidative Stress and Cerebral Vascular Tone: The Role of Reactive Oxygen and Nitrogen Species.

The brain's unique characteristics make it exceptionally susceptible to oxidative stress, which arises from an imbalance between reactive oxygen species (ROS) production, reactive nitrogen species (RNS) production, and antioxidant defense mechanisms. This review explores the factors contributing to the brain's vascular tone's vulnerability in the presence of oxidative damage, which can be of clinical interest in critically ill patients or those presenting acute brain injuries. The brain's high metabolic rate and inefficient electron transport chain in mitochondria lead to significant ROS generation. Moreover, non-replicating neuronal cells and low repair capacity increase susceptibility to oxidative insult. ROS can influence cerebral vascular tone and permeability, potentially impacting cerebral autoregulation. Different ROS species, including superoxide and hydrogen peroxide, exhibit vasodilatory or vasoconstrictive effects on cerebral blood vessels. RNS, particularly NO and peroxynitrite, also exert vasoactive effects. This review further investigates the neuroprotective effects of antioxidants, including superoxide dismutase (SOD), vitamin C, vitamin E, and the glutathione redox system. Various studies suggest that these antioxidants could be used as adjunct therapies to protect the cerebral vascular tone under conditions of high oxidative stress. Nevertheless, more extensive research is required to comprehensively grasp the relationship between oxidative stress and cerebrovascular tone, and explore the potential benefits of antioxidants as adjunctive therapies in critical illnesses and acute brain injuries.

Serum LDH levels may predict poor neurological outcome after aneurysmal subarachnoid hemorrhage.

INTRODUCTION: Serum lactate dehydrogenase (LDH) levels are often elevated in cardiovascular diseases. Their prognostic role after subarachnoid hemorrhage (SAH) remains poorly evaluated. METHODS: This is a retrospective single-center study of patients with non-traumatic SAH admitted to the intensive care unit (ICU) of an University Hospital from 2007 to 2022. Exclusion criteria were pregnancy and incomplete medical records or follow-up data. Baseline information, clinical data, radiologic data, the occurrence of neurological complications as well as serum LDH levels during the first 14 days of ICU stay were collected. Unfavorable neurological outcome (UO) at 3 months was defined as a Glasgow Outcome Scale of 1-3. RESULTS: Five hundred and forty-seven patients were included; median serum LDH values on admission and the highest LDH values during the ICU stay were 192 [160-230] IU/L and 263 [202-351] IU/L, respectively. The highest LDH value was recorded after a median of 4 [2-10] days after ICU admission. LDH levels on admission were significantly higher in patients with UO. When compared with patients with favorable outcome (FO), patients with UO had higher serum LDH values over time. In the multivariate logistic regression model, the highest LDH value over the ICU stay (OR 1.004 [95% CI 1.002 - 1.006]) was independently associated with the occurrence of UO; the area under the receiving operator (AUROC) curve for the highest LDH value over the ICU stay showed a moderate accuracy to predict UO (AUC 0.76 [95% CI 0.72-0.80]; p < 0.001), with an optimal threshold of > 272 IU/L (69% sensitivity and 74% specificity). CONCLUSIONS: The results in this study suggest that high serum LDH levels are associated with the occurrence of UO in SAH patients. As a readily and available biomarker, serum LDH levels should be evaluated to help with the prognostication of SAH patients.

Can artificial intelligence help for scientific writing?

This paper discusses the use of Artificial Intelligence Chatbot in scientific writing. ChatGPT is a type of chatbot, developed by OpenAI, that uses the Generative Pre-trained Transformer (GPT) language model to understand and respond to natural language inputs. AI chatbot and ChatGPT in particular appear to be useful tools in scientific writing, assisting researchers and scientists in organizing material, generating an initial draft and/or in proofreading. There is no publication in the field of critical care medicine prepared using this approach; however, this will be a possibility in the next future. ChatGPT work should not be used as a replacement for human judgment and the output should always be reviewed by experts before being used in any critical decision-making or application. Moreover, several ethical issues arise about using these tools, such as the risk of plagiarism and inaccuracies, as well as a potential imbalance in its accessibility between high- and low-income countries, if the software becomes paying. For this reason, a consensus on how to regulate the use of chatbots in scientific writing will soon be required.

Cervical Ganglion Sympathectomy to Treat Cerebral Vasospasm in Subarachnoid Hemorrhage.

Delayed cerebral ischemia (DCI) is still a significant cause of death and disability after aneurysmal subarachnoid hemorrhage. Cerebral vasospasm represents one of the most reported mechanisms associated with DCI. The management of DCI-related vasospasm remains a significant challenge for clinicians; induced hypertension, intraarterial vasodilators, and/or intracranial vessel angioplasty-particularly in refractory or recurrent cases-are the most used therapies. Because an essential role in the pathophysiology of cerebral vasospasm has been attributed to the adrenergic sympathetic nerves, a "sympatholytic" intervention, consisting of a temporary interruption of the sympathetic pathways using local anesthetics, has been advocated to minimize the vascular narrowing and reverse the consequences of cerebral vasospasm on tissue perfusion. In this review, we have analyzed the existing literature on the block of the cervical ganglions, particularly the stellate ganglion, in managing refractory cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage. These findings could help clinicians to understand the potential role of such intervention and to develop future interventional trials in this setting.

A practical guide to patient position and complication management in neurosurgery: a systematic qualitative review.

PURPOSE: Adequate patient positioning is of paramount importance in neurosurgery. Complications related to the position are common and make up for more than 16% of the claims towards anaesthesiologists and neurosurgeons. This paper aims to provide the anaesthesiologist with a practical guide to avoid common pitfalls related to the patient positioning process. METHOD: We performed a systematic review of the medical literature for the identification, screening, and inclusion of articles. The bibliographic search was conducted on June 1st, 2021 by two of the authors. In this review, we included articles indexed by MEDLINE, Cochrane Library, or Google Scholar. RESULTS: We retrieved a total of 5706 unique papers from our initial search. However, after the initial screening, 5363 papers were removed is not related to our research leaving a total of 343 papers. We examined the full text of all the 343 articles including 68 of them in the final qualitative analysis. DISCUSSION: In this review we examine the most common neurosurgical positions: supine, sitting, lateral, park-bench, prone, jack-knife, and knee-chest. For each of them, the proper positioning and related complications are described. Particular attention is given to the prevention and management of these complications, providing a practical guide for clinicians.

The Normobaric Oxygen Paradox-Hyperoxic Hypoxic Paradox: A Novel Expedient Strategy in Hematopoiesis Clinical Issues.

Hypoxia, even at non-lethal levels, is one of the most stressful events for all aerobic organisms as it significantly affects a wide spectrum of physiological functions and energy production. Aerobic organisms activate countless molecular responses directed to respond at cellular, tissue, organ, and whole-body levels to cope with oxygen shortage allowing survival, including enhanced neo-angiogenesis and systemic oxygen delivery. The benefits of hypoxia may be evoked without its detrimental consequences by exploiting the so-called normobaric oxygen paradox. The intermittent shift between hyperoxic-normoxic exposure, in addition to being safe and feasible, has been shown to enhance erythropoietin production and raise hemoglobin levels with numerous different potential applications in many fields of therapy as a new strategy for surgical preconditioning aimed at frail patients and prevention of postoperative anemia. This narrative review summarizes the physiological processes behind the proposed normobaric oxygen paradox, focusing on the latest scientific evidence and the potential applications for this strategy. Future possibilities for hyperoxic-normoxic exposure therapy include implementation as a synergistic strategy to improve a patient's pre-surgical condition, a stimulating treatment in critically ill patients, preconditioning of athletes during physical preparation, and, in combination with surgery and conventional chemotherapy, to improve patients' outcomes and quality of life.

Modulation of red blood cell oxygen affinity with a novel allosteric modifier of hemoglobin is additive to the Bohr effect.

PURPOSE: The Bohr effect describes hemoglobin's affinity for oxygen dependent on solution pH. Within pH range 6.0-8.5, hemoglobin's oxygen affinity decreases with decreasing pH. This results in increased oxygen delivery to metabolically active, acidic tissues and improved oxygen uptake in basic regions including lung tissue. Myo-Inositol tripyrophosphate (ITPP) translocates the erythrocyte membrane and allosterically modifies hemoglobin (Hb). We tested the hypothesis that ITPP does not abrogate the Bohr effect. METHODS: Experiments were conducted to determine the effect of increasing concentrations of ITPP on P50 with varying pH. We incubated 10 mL red blood cells at 37 °C for 1 h with ITPP concentrations from 0 to 240 mM. The Clark oxygen electrode (Hemox-Analyzer; TCS Scientific, New Hope, PA) determined oxygen affinity of each sample, in triplicate, using buffers pH 6.8, 7.4, and 7.6. A mixed linear regression model with fixed effects for ITPP concentration and pH was used. RESULTS: Increasing ITPP concentration and decreasing pH increased P50 (p < 0.0001 for ITPP concentration, p < 0.0001 for pH). ITPP modulated increased P50 in normal pH (7.4) and acidic condition pH (6.8); with no effect at alkaline pH (7.6). CONCLUSION: The Bohr effect is conserved, with ITPP augmenting the decreased oxygen affinity seen with tissue acidosis, while not affecting oxygen affinity in conditions similar to a pulmonary microenvironment.

Breast Regional Anesthesia Practice in the Italian Public Health System (BRA-SURVEY): A Survey-Based National Study.

BACKGROUND: Breast cancer is the most common malignancy in women. Surgery is a mainstay therapy unfortunately burdened by complications as severe postoperative pain. Regional anesthesia may play a role in a multimodal strategy for prevention and treatment of postoperative pain. The main purpose of this survey was to investigate the rate of use of regional anesthesia techniques in patients undergoing breast surgery in the Italian public hospital system. METHODS: We designed an online survey that consisted of 22 questions investigating the anesthesia management of breast surgery, particularly focused on regional anesthesia. The survey lasted from November 18, 2019 to February 28, 2020. Directors of anesthesia departments of 168 Italian public health system hospitals were contacted and invited to forward the survey to every anesthesiologist in their unit. RESULTS: A total of 935 anesthesiologists received the survey; among them 460 entered the final analysis. Regional anesthesia was not used by 44.6% of the anesthesiologists and lack of experience/training was the main cause (75.6%). Logistic regression models revealed that anesthesiologists with more than 15 years of experience (odds ratio [OR] = 0.55; 95% confidence interval [CI], 0.33-0.93) or working most of their days in intensive care unit (ICU) compared to operating theater (OR = 0.25; 95% CI, 0.14-0.43) were less likely to perform regional anesthesia techniques. CONCLUSIONS: Low implementation of regional anesthesia techniques in breast surgery emerges from our survey and the major reason cited is a lack of proper training. An improved training program in regional anesthesia, especially in residents' curricula, could be useful to increase its rate of use and to standardize its practice.

Influence of the type of congenital heart defects on epithelial lining fluid composition in infants undergoing cardiac surgery with cardiopulmonary bypass.

BackgroundIn children with congenital heart disease (CHD), altered pulmonary circulation compromises gas exchange. Moreover, pulmonary dysfunction is a complication of cardiac surgery with cardiopulmonary bypass (CPB). No data are available on the effect of different CHDs on lung injury. The aim of this study was to analyze epithelial lining fluid (ELF) surfactant composition in children with CHD.MethodsTracheal aspirates (TAs) from 72 CHD children (age 2.9 (0.4-5.7) months) were obtained before and after CPB. We measured ELF phospholipids, surfactant proteins A and B (SP-A, SP-B), albumin, and myeloperoxidase activity. TAs from 12 infants (age 1.0 (0.9-2.9) months) with normal heart/lung served as controls.ResultsHeart defects were transposition of great arteries (19), tetralogy of Fallot (TOF, 20), atrial/ventricular septal defect (ASD/VSD, 22), and hypoplastic left heart syndrome (11). Increased levels of ELF SP-B were found in all defects, increased myeloperoxidase activity in all except the TOF, and increased levels of ELF albumin and SP-A only in ASD/VSD patients. Postoperatively, ELF findings remained unchanged except for a further increase in myeloperoxidase activity.ConclusionELF composition has distinctive patterns in different CHD. We speculate that a better knowledge of the ELF biochemical changes may help to prevent respiratory complications.

Exploring the effects of post operative hyperoxic intermittent stimuli on reticulocyte levels in cancer patients: a randomized controlled study.

BACKGROUND: Anemia is common among hospitalized critically ill and surgical oncological patients. The rising incidence of cancer and aggressive treatments has increased the demand for blood products, further strained by a dwindling donor pool. The normobaric oxygen paradox (NOP) has emerged as a potential avenue to increase EPO levels. While some studies support its efficacy, research remains limited in clinical settings. This study aims to assess the effectiveness of a NOP protocol in stimulating erythropoiesis, as measured by changes in reticulocyte counts, in cancer patients undergoing abdominal surgeries. METHODS: This is a post hoc analysis of a prospective, single-center, controlled, randomized study. A total of 49 patients undergoing abdominal surgery were analyzed at the Institut Jules Bordet. Adult patients admitted to the intensive care unit (ICU) for at least 24 h were enrolled, excluding those with severe renal insufficiency or who received transfusions during the study period. Participants were randomized into two groups: a normobaric oxygen paradox (OXY) group who received 60% oxygen for 2 h on days 1, 3, and 5 post-surgery and a control (CTR) group who received standard care. Data on baseline characteristics, surgical details, and laboratory parameters were collected. Statistical analysis included descriptive statistics, chi-square tests, t-tests, Mann-Whitney tests, and linear and logistic regression. RESULTS: The final analysis included 33 patients (median age 62 [IQR 58-66], 28 (84.8%) males, with no withdrawals or deaths during the study period. No significant differences were observed in baseline surgical characteristics or perioperative outcomes between the two groups. In the OXY group (n = 16), there was a significant rise (p = 0.0237) in the percentage of reticulocyte levels in comparison to the CTR group (n = 17), with median values of 36.1% (IQR 20.3-57.8) versus - 5.3% (IQR - 19.2-57.8), respectively. The increases in hemoglobin and hematocrit levels did not significantly differ between the groups when compared to their baselines' values. CONCLUSIONS: This study provides preliminary evidence supporting the potential of normobaric oxygen therapy in stimulating erythropoiesis in cancer patients undergoing abdominal surgeries. While the OXY group resulted in increased reticulocyte counts, further research with larger sample sizes and multi-center trials is warranted to confirm these findings. TRIAL REGISTRATION: The study was retrospectively registered under NCT number 06321874 on The 10th of April 2024.

Brain hemodynamics in septic patients.

Brain dysfunction is a frequent complication of sepsis. Most likely, sepsis-associated brain dysfunction (SABD) results from the interaction between multiple factors: neurodegeneration due to microglial activation, altered neurotransmission, neuroinflammation and impairment of cerebral macro- and microcirculation. Altered brain perfusion might results from several mechanism: global or regional alterations in cerebral blood flow (CBF); reduced cerebral perfusion pressure - which is the driving force propelling blood through cerebral blood vessels - due to systemic hypotension; global or regional vasoconstriction; dysfunction of the intrinsic regulatory mechanisms of CBF, such as cerebral autoregulation and cerebrovascular reactivity; endothelial and blood-brain barrier dysfunction; autonomic nervous system dysfunction and metabolic uncoupling. Disorders of brain perfusion and CBF regulation are frequently observed in humans with sepsis, and intracranial hemodynamics monitoring can potentially be useful in clinical management of septic patients. The aim of this review is to provide an update of the current knowledge on alterations in brain hemodynamics associated with sepsis, along with physiological and methodological considerations intended to help the reader navigate the diverse results from published literature and a practical guide to apply non-invasive intracranial hemodynamics monitoring to septic patients in clinical practice.