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The pathophysiological underpinnings of critically disrupted brain connectomes resulting in coma are poorly understood. Inflammation is potentially an important but still undervalued factor. Here, we present a first-in-human prospective study using the 18-kDa translocator protein (TSPO) radioligand 18F-DPA714 for PET imaging to allow in vivo neuroimmune activation quantification in patients with coma (n = 17) following either anoxia or traumatic brain injuries in comparison with age- and sex-matched controls. Our findings yielded novel evidence of an early inflammatory component predominantly located within key cortical and subcortical brain structures that are putatively implicated in consciousness emergence and maintenance after severe brain injury (i.e. mesocircuit and frontoparietal networks). We observed that traumatic and anoxic patients with coma have distinct neuroimmune activation profiles, both in terms of intensity and spatial distribution. Finally, we demonstrated that both the total amount and specific distribution of PET-measurable neuroinflammation within the brain mesocircuit were associated with the patient's recovery potential. We suggest that our results can be developed for use both as a new neuroprognostication tool and as a promising biometric to guide future clinical trials targeting glial activity very early after severe brain injury.
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Lesões Encefálicas , Coma Pós-Traumatismo da Cabeça , Humanos , Coma/complicações , Coma Pós-Traumatismo da Cabeça/complicações , Estudos Prospectivos , Imageamento por Ressonância Magnética/métodos , Encéfalo/metabolismo , Lesões Encefálicas/complicações , Hipóxia/complicações , Receptores de GABA/metabolismoRESUMO
INTRODUCTION: Pain related to injection of propofol during induction of anesthesia decreases from 66.8% without prevention, to 22-31% of cases when lidocaine is associated. Hypnoanalgesia of the hand is currently used for painful procedures in children but has never been evaluated in this indication. The primary aim of this prospective randomized single-blind study was to evaluate the efficacy of hypnoanalgesia of the hand for the prevention of moderate to severe pain during intravenous injection of propofol alone in comparison to lidocaine admixture. The secondary aim was to compare the global satisfaction of children in both methods. PATIENTS AND METHODS: One hundred patients aged 7-14 years, ASA 1-2, admitted for scheduled surgery under general anesthesia were randomized into two groups. Group L received a mixture of 1% propofol (3 mg/kg) and 1% Lidocaine (0.3 mg/kg). Group H received 1% propofol (3 mg/kg) after hypnoanalgesia of the hand realized by a single experimented operator. A video was made in order to evaluate the pain related to propofol injection by a blinded observer using the 4-point score of Cameron (painful ≥ 2). The global satisfaction of children was evaluated in postanesthesia care unit and documented if visual analog score was <7/10. RESULTS: Ninety-six patients were analyzed. The rate of painful patients did not differ significantly between groups (8.5% in group H [n = 47] vs 6.1% in group L [n = 49], OR= 0.70; 95% CI [0.13-3.35], p = 0.65), nor did the rate of nonsatisfied patients (10.6 in group H vs. 12.2% in group L, OR = 0.85; 95% CI [0.19-3.65], p = 1). CONCLUSIONS: Our results suggest that hypnoanalgesia of the hand alone is effective to prevent the pain related to propofol injection in children. No significant difference was found in comparison with lidocaine admixture nor for pain or satisfaction.
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Anestésicos Intravenosos , Anestésicos Locais , Mãos , Lidocaína , Dor , Propofol , Humanos , Lidocaína/administração & dosagem , Propofol/administração & dosagem , Criança , Feminino , Masculino , Adolescente , Método Simples-Cego , Estudos Prospectivos , Dor/prevenção & controle , Anestésicos Locais/administração & dosagem , Anestésicos Intravenosos/administração & dosagem , Anestésicos Intravenosos/efeitos adversos , Mãos/cirurgia , Injeções Intravenosas , Satisfação do Paciente , Medição da Dor/métodos , Anestesia PediátricaRESUMO
There is general agreement that acute pain management is an important component of perioperative medicine. However, there is no consensus on the best model of care for perioperative pain management, mainly because evidence is missing in many aspects. Comparing the similarities and differences between countries might reveal some insights into different organisational models and how they work. Here, we performed a narrative review to describe and compare the structures, processes and outcomes of perioperative pain management in the healthcare systems of four European countries using Donabedian's framework as a guide. Our comparison revealed many similarities, differences and gaps. Different structures of acute pain services in the four countries with no common definition and standards of care were found. Protocols have been implemented in all countries and guidelines in some. If outcome is assessed, it is mainly pain intensity, and many patients experiencing more intense pain than others have common risk factors (e.g. preoperative pain, preoperative opioid intake, female sex and young age). Outcome assessment beyond pain intensity (such as pain-related physical function, which is important for early rehabilitation and recovery) is currently not well implemented. Developing common quality indicators, a European guideline for perioperative pain management (e.g. for patients at high risk for experiencing severe pain and other outcome parameters) and common criteria for acute pain services might pave the way forward for improving acute pain management in Europe. Finally, the education of general and specialist staff should be aligned in Europe, for example, by using the curricula of the European Pain Federation (EFIC).
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Analgésicos Opioides , Manejo da Dor , Humanos , Feminino , Europa (Continente) , Analgésicos Opioides/efeitos adversos , DorRESUMO
BACKGROUND: Renal artery Doppler sonography with resistive index (RI) determination is a noninvasive, fast, and reliable diagnostic tool increasingly used in the intensive care unit (ICU) to predict and assess the reversibility of acute kidney injury (AKI). However, interpreting the RI can be challenging due to numerous influencing factors. While some studies have explored various confounding factors, arterial blood gases have received limited attention. Therefore, our study aims to evaluate the impact of arterial blood gases on the RI in the ICU setting. METHODS: This prospective observational study enrolled ICU patients who required blood gas analysis and had not experienced significant hemodynamic changes recently. The RI was measured using standardized Doppler ultrasound within an hour of the arterial blood gases sampling and analysis. RESULTS: A total of sixty-four patients were included in the analysis. Univariate analysis revealed a correlation between the RI and several variables, including PaCO2 (R = 0.270, p = 0.03), age (R = 0.574, p < 0.0001), diastolic arterial pressure (DAP) (R = - 0.368, p = 0.0028), and SaO2 (R = - 0.284, p = 0.0231). Multivariate analysis confirmed that age > 58 years and PaCO2 were significant factors influencing the RI, with respective odds ratios of 18.67 (p = 0.0003) and 1.132 (p = 0.0267). CONCLUSION: The interpretation of renal arterial RI should take into account thresholds for PaCO2, age, and diastolic arterial pressure. Further studies are needed to develop a comprehensive scoring system that incorporates all these cofactors for a reliable analysis of RI levels. Trial registration This observational study, registered under number 70-0914, received approval from local Ethical Committee of Toulouse University Hospital.
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Injúria Renal Aguda , Rim , Humanos , Pessoa de Meia-Idade , Rim/irrigação sanguínea , Unidades de Terapia Intensiva , Gasometria , GasesRESUMO
INTRODUCTION: The COVID-19 pandemic has prompted the development of anesthesia teleconsultation in many countries. In pediatric anesthesia, data about anesthesia teleconsultation are scarce. The main objective of this prospective descriptive study was to provide an evaluation of the feasibility of pediatric anesthesia teleconsultation. Perception of the safety and quality, parental and medical satisfaction were also assessed. METHODS: From September to December 2020, patients undergoing a pediatric anesthesia teleconsultation in Toulouse University Hospital, using the TeleO™ dedicated teleconsultation platform were prospectively included. Feasibility was defined as the rate of anesthesia teleconsultations successfully performed using the TeleO™ platform alone. Questionnaires regarding the quality, safety, and satisfaction were filled in by physicians and families. RESULTS: A total of 114 children (3 months-17 years) were included in the study. Feasibility was 82%, failure was mainly caused by technical issues. Physicians estimated that the safety and quality of anesthetic preparation were optimal in 100% of cases. Anesthetists were satisfied (VAS ≥70/100) with the medical, technical, and relational (child/parents) aspects of anesthesia teleconsultation in 91%, 64%, and 84%/90% of cases respectively. Almost all parents (97%) stated that they would agree to anesthesia teleconsultation for a future procedure. CONCLUSION: In this first assessment, pediatric anesthesia teleconsultation appears to be feasible, with high rates of medical and parental satisfaction. Physicians' perception of the safety and quality of this process were positive. Improving the technical process might be a key determinant to promote further development of pediatric anesthesia teleconsultation.
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Anestesia , COVID-19 , Consulta Remota , Telemedicina , Criança , Humanos , Consulta Remota/métodos , Telemedicina/métodos , Estudos de Viabilidade , Pandemias , Satisfação Pessoal , FrançaRESUMO
PURPOSE: The use of regional anesthesia (RA) for anterior cruciate ligament (ACL) reconstruction reduces morphine consumption, the time spent in the post-anesthesia care unit (PACU) and the hospital readmission rate. However, RA failures due to delays in the induction of anesthesia and its unpredictable success rate (Cuvillon et al. Ann Fr Anesth 29:710-715, 2010; Jankowski et al. Anesth Analg 10.1213/01.ANE.0000081798.89853.E7) can lead to disorganization of the operating room (OR) schedule. The hypothesis is that performing RA outside the OR will significantly reduce the OR occupancy time relative to using general anesthesia (GA). The primary objective was to compare the OR occupancy time between RA and GA when performing ACL reconstruction. METHODS: This was a retrospective, single-center study of data collected prospectively from consecutive patients operated by a single surgeon between January 2019 and December 2020. The patients undergoing ACL reconstruction were divided into two groups based on the type of anesthesia they received (GA, RA). RA consisted of a quadruple peripheral nerve block (femoral, sciatic, obturator and lateral femoral cutaneous nerves). The durations of the perioperative stages of the patient's journey in the OR suite were compared between these two groups. RESULTS: The analysis involved 469 ACL reconstructions: 356 GA and 113 RA. The two groups were comparable in age, gender and ASA score (American Society of Anesthesiologists). The OR occupancy time for ACL reconstruction with RA was reduced by a mean of 13 min (70 ± 12 SD vs. 83 ± 14 SD; P < 0.0001) and the PACU time by 41 min relative to GA (P < 0.0001). The entry-incision time was reduced by an average of 8 min and the end-exit time by 3 min (P < 0.0001). The care time in the PACU was reduced from 84 ± 35 to 46 ± 26 min (P < 0.0001). However, performing anesthesia outside the OR (i.e., in a RA block room) did not reduce the turnover time (n.s). CONCLUSION: Performing RA outside the OR reduced the OR occupancy time by nearly 20% relative to using GA for ACL reconstructions. LEVEL OF EVIDENCE: Level IV.
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Anestesia por Condução , Reconstrução do Ligamento Cruzado Anterior , Bloqueio Nervoso , Humanos , Salas Cirúrgicas , Estudos Retrospectivos , Plexo LombossacralRESUMO
BACKGROUND: The delayed diagnosis of acute kidney injury (AKI) episodes and the lack of specificity of current single AKI biomarkers hamper its management. Urinary peptidome analysis may help to identify early molecular changes in AKI and grasp its complexity to identify potential targetable molecular pathways. METHODS: In derivation and validation cohorts totalizing 1170 major cardiac bypass surgery patients and in an external cohort of 1569 intensive care unit (ICU) patients, a peptide-based score predictive of AKI (7-day KDIGO classification) was developed, validated, and compared to the reference biomarker urinary NGAL and NephroCheck and clinical scores. RESULTS: A set of 204 urinary peptides derived from 48 proteins related to hemolysis, inflammation, immune cells trafficking, innate immunity, and cell growth and survival was identified and validated for the early discrimination (< 4 h) of patients according to their risk to develop AKI (OR 6.13 [3.96-9.59], p < 0.001) outperforming reference biomarkers (urinary NGAL and [IGFBP7].[TIMP2] product) and clinical scores. In an external cohort of 1569 ICU patients, performances of the signature were similar (OR 5.92 [4.73-7.45], p < 0.001), and it was also associated with the in-hospital mortality (OR 2.62 [2.05-3.38], p < 0.001). CONCLUSIONS: An overarching AKI physiopathology-driven urinary peptide signature shows significant promise for identifying, at an early stage, patients who will progress to AKI and thus to develop tailored treatments for this frequent and life-threatening condition. Performance of the urine peptide signature is as high as or higher than that of single biomarkers but adds mechanistic information that may help to discriminate sub-phenotypes of AKI offering new therapeutic avenues.
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Injúria Renal Aguda , Humanos , Lipocalina-2 , Valor Preditivo dos Testes , Injúria Renal Aguda/diagnóstico , Biomarcadores , PeptídeosRESUMO
During severe sepsis, platelet activation may induce disseminate microvascular thrombosis, which play a key role in critical organ failure. Crucially, most of the studies in this field have explored platelet-leukocyte interactions in animal models, or explored platelets under the spectrum of thrombocytopenia or disseminated intravascular coagulation and have not taken into account the complex interplay that might exist between platelets and leukocytes during human septic shock nor the kinetics of platelet activation. Here, we assessed platelet activation parameters at the admission of patients with sepsis to the intensive care unit (ICU) and 48 hours later. Twenty-two patients were enrolled in the study, thirteen (59.1%) of whom were thrombocytopenic. The control group was composed of twelve infection-free patients admitted during the study period. The activation parameters studied included platelet-leukocyte interactions, assessed by flow cytometry in whole blood, as well as membrane surface and soluble platelet activation markers measured by flow cytometry and dedicated ELISA kits. We also investigated platelet aggregation and secretion responses of patients with sepsis following stimulation, compared to controls. At admission, the level of circulating monocyte-platelet and neutrophil-platelet heterotypic aggregates was significantly higher in sepsis patients compared to controls and returned to a level comparable to controls or even below 48 hours later. Basal levels of CD62P and CD63 platelet membrane exposure at admission and 48 hours later were low and similar to controls. In contrast, plasma level of soluble GPVI and soluble CD40 ligand was significantly increased in septic patients, at the two times of analysis, reflecting previous platelet activation. Platelet aggregation and secretion responses induced by specific agonists were significantly decreased in septic conditions, particularly 48 hours after admission. Hence, we have observed for the first time that critically ill septic patients compared to controls have both an early and durable platelet activation while their circulating platelets are less responsive to different agonists.
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Sepse , Choque Séptico , Animais , Plaquetas/fisiologia , Humanos , Unidades de Terapia Intensiva , Ativação Plaquetária/fisiologiaRESUMO
INTRODUCTION: The transition from medical student to surgical resident is not a simple one. The aim of this study was to report the experience of a university hospital in the organization of the induction course for future surgical residents and the contribution of a video support in the learning of the suture. MATERIAL AND METHOD: We were able to study two consecutive years of students (October 2020 and 2021). Concerning the practical and technical workshops (learning suture) we carried out a comparative study between two groups of students. A group that had video support for learning suture (video group) and a group without video (control group). The evaluation of the suture was performed in a blinded manner by two supervising surgeons. The other practical workshop was drain fixation; the students did not have a video for this workshop. A comparative study was also performed for the drain fixation workshop between the two groups (video group and control group). A program of theoretical courses was also set up. This program is established according to the different future functions of the residents by integrating medico-legal notions and teamwork. Satisfaction questionnaires were given to the students and the answers were given two months after taking up their duties in the hospital (6 questions with Likert scale and 4 free questions). RESULTS: The cohort consisted of 58 students (29 each in 2020 and 29 in 2021). Comparative analyses of the evaluation of the suture workshops showed better performance in the video group compared with the group without video. The comparison of these two groups did not show significant differences in the drain fixation workshop. The theoretical teaching was broken down according to the students' future tasks and each speaker was a specialist in his or her field of expertise. The results of the questionnaires showed a desire on the part of the students to increase the time spent on practical workshops and theoretical forensic teaching. CONCLUSION: We were able to show through these two years of a program that we were able to offer a surgical resident preparation course. In addition, we have highlighted the contribution of a video support in the learning curve of the suture.
Assuntos
Internato e Residência , Estudantes de Medicina , Avaliação Educacional , Retroalimentação , Feminino , Hospitais Universitários , Humanos , MasculinoRESUMO
OBJECTIVES: Patients on venoarterial extracorporeal membrane oxygenation have many risk factors for pulmonary complications in addition to their heart failure. Optimal positive end-expiratory pressure is unknown in these patients. The aim was to evaluate the ability of electrical impedance tomography to help the physician to select the optimal positive end-expiratory pressure in venoarterial extracorporeal membrane oxygenation treated and mechanically ventilated patients during a positive end-expiratory pressure trial. DESIGN: Observational prospective monocentric. SETTING: University hospital. PATIENTS: Patients (n = 23) older than 18 years old, on mechanical ventilation and venoarterial extracorporeal membrane oxygenation. INTERVENTIONS: A decreasing positive end-expiratory pressure trial (20-5 cm H2O) in increments of 5 cm H2O was performed and monitored by a collection of clinical parameters, ventilatory and ultrasonographic (cardiac and pulmonary) to define an optimal positive end-expiratory pressure according to respiratory criteria (optimal positive end-expiratory pressure selected by physician with respiratory parameters), and then adjusted according to hemodynamic and cardiac tolerances (optimal positive end-expiratory pressure selected by physician with respiratory, hemodynamic, and echocardiographic parameters). At the same time, electrical impedance tomography data (regional distribution of ventilation, compliance, and overdistension collapse) were recorded and analyzed retrospectively to define the optimal positive end-expiratory pressure. MEASUREMENTS AND MAIN RESULTS: The median of this optimal positive end-expiratory pressure was 10 cm H2O in our population. Electrical impedance tomography showed that increasing positive end-expiratory pressure promoted overdistention of ventral lung, maximum at positive end-expiratory pressure 20 cm H20 (34% [interquartile range, 24.5-40]). Decreasing positive end-expiratory pressure resulted in collapse of dorsal lung (29% [interquartile range, 21-45.8]). The optimal positive end-expiratory pressure selected by physician with respiratory parameters was not different from the positive end-expiratory pressure chosen by the electrical impedance tomography. However, there is a negative impact of a high level of intrathoracic pressure on hemodynamic and cardiac tolerances. CONCLUSIONS: Our results support that electrical impedance tomography appears predictive to define optimal positive end-expiratory pressure on venoarterial extracorporeal membrane oxygenation, aided by echocardiography to optimize hemodynamic assessment and management.
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Impedância Elétrica , Oxigenação por Membrana Extracorpórea/métodos , Respiração com Pressão Positiva/métodos , Adulto , Idoso , Feminino , Nível de Saúde , Hemodinâmica , Hospitais Universitários , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Mecânica RespiratóriaRESUMO
Recent European Society of Parenteral and Enteral Nutrition guidelines highlighted the interest of prevention, diagnosis and treatment of malnutrition in the management of coronavirus disease 19 (COVID-19) patients. The aim of our study was to evaluate the prevalence of malnutrition in patients hospitalised for COVID-19. In a prospective observational cohort study malnutrition was diagnosed according to the Global Leadership Initiative on Malnutrition (GLIM) two-step approach. Patients were divided into two groups according to the diagnosis of malnutrition. Covariate selection for the multivariate analysis was based on P <0·2 in univariate analysis, with a logistic regression model and a backward elimination procedure. A partitioning of the population was realised. Eighty patients were prospectively enrolled. Thirty patients (37·5 %) had criteria for malnutrition. The need for intensive care unit admission (n 46, 57·5 %) was similar in the two groups. Three patients who died (3·75 %) were malnourished. Multivariate analysis exhibited that low BMI (OR 0·83, 95 % CI 0·73, 0·96, P = 0·0083), dyslipidaemia (OR 29·45, 95 % CI 3·12, 277·73, P = 0·0031), oral intake reduction <50 % (OR 3·169, 95 % CI 1·04, 9·64, P = 0·0422) and glomerular filtration rate (Chronic Kidney Disease Epidemiology Collaboration; CKD-EPI) at admission (OR 0·979, 95 % CI 0·96, 0·998, P = 0·0297) were associated with the occurrence of malnutrition. We demonstrate the existence of a high prevalence of malnutrition in a general cohort of COVID-19 inpatients according to GLIM criteria. Nutritional support in COVID-19 care seems an essential element.
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COVID-19/complicações , Pacientes Internados/estatística & dados numéricos , Desnutrição/epidemiologia , SARS-CoV-2 , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Modelos Logísticos , Masculino , Desnutrição/virologia , Pessoa de Meia-Idade , Avaliação Nutricional , Prevalência , Estudos Prospectivos , Adulto JovemRESUMO
BACKGROUND: The long-term fate of severely injured patients in terms of their quality of life is not well known. Our aim was to assess the quality of life of patients who have suffered moderate to severe trauma and to identify primary factors of long-term quality of life impairment. METHODS: A prospective monocentric study conducted on a number of patients who were victims of moderate to severe injuries during the year 2012. Patients were selected based on an Injury Severity Score (ISS) more than or equal to 9. Quality of life was assessed by the MOS SF-36 and NHP scores as a primary evaluation criterion. The secondary evaluation criteria were the determination of the socio-economic impact on quality of life and the identification of factors associated with disability. RESULTS: Two hundred and eight patients were contacted by e-mail or telephone. Fifty-five patients participated in this study (with a participation level of 26.4%), including 78.2% men, with a median age of 46. Significant alterations in quality of life were observed with the NHP and MOS SF-36 scale, including physical and psychological components. This resulted in a major socio-economic impact as 26% of the patients could not resume their professional activities (n = 10), 20% required retraining in other lines of work, and 36.4% had a disability status. The study showed that scores ≤ 85 on the physical functioning variable of the MOS SF 36 scale was associated with disability. CONCLUSION: More than five years after a moderate to severe injury, patients' quality of life was significantly impacted, resulting in significant socio-economic consequences. Disability secondary to major trauma seems to be associated with a score ≤ 85 on the physical functioning dimension of the MOS SF-36 scale. This study raises the question of whether or not early rehabilitation programs should be implemented in order to limit the long-term impact of major trauma.
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Pessoas com Deficiência/psicologia , Pessoas com Deficiência/estatística & dados numéricos , Qualidade de Vida/psicologia , Ferimentos e Lesões/psicologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , França , Humanos , Escala de Gravidade do Ferimento , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto JovemRESUMO
Different dosage regimens of hydroxychloroquine are used to manage coronavirus disease 2019 (COVID-19) patients, without information on the pharmacokinetics in this population. Blood samples (nâ =â 101) were collected from 57 COVID-19 patients for 7 days, and concentrations were compared with simulated kinetic profiles. Hydroxychloroquine exposure is low and cannot be predicted by other populations.
Assuntos
Antivirais , Tratamento Farmacológico da COVID-19 , Antivirais/uso terapêutico , Humanos , Hidroxicloroquina/uso terapêutico , Cinética , SARS-CoV-2RESUMO
OBJECTIVES: Recovery from coma might critically depend on the structural and functional integrity of frontoparietal networks. We aimed to measure this integrity in traumatic brain injury and anoxo-ischemic (cardiac arrest) coma patients by using an original multimodal MRI protocol. DESIGN: Prospective cohort study. SETTING: Three Intensive Critical Care Units affiliated to the University in Toulouse (France). PATIENTS: We longitudinally recruited 43 coma patients (Glasgow Coma Scale at the admission < 8; 29 cardiac arrest and 14 traumatic brain injury) and 34 age-matched healthy volunteers. Exclusion criteria were disorders of consciousness lasting more than 30 days and focal brain damage within the explored brain regions. Patient assessments were conducted at least 2 days (5 ± 2 d) after complete withdrawal of sedation. All patients were followed up (Coma Recovery Scale-Revised) 3 months after acute brain injury. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Functional and structural MRI data were recorded, and the analysis was targeted on the posteromedial cortex, the medial prefrontal cortex, and the cingulum. Univariate analyses and machine learning techniques were used to assess diagnostic and predictive values. Coma patients displayed significantly lower medial prefrontal cortex-posteromedial cortex functional connectivity (area under the curve, 0.94; 95% CI, 0.93-0.95). Cardiac arrest patients showed specific structural disturbances within posteromedial cortex. Significant cingulum architectural disturbances were observed in traumatic brain injury patients. The machine learning medial prefrontal cortex-posteromedial cortex multimodal classifier had a significant predictive value (area under the curve, 0.96; 95% CI, 0.95-0.97), best combination of subregions that discriminates a binary outcome based on Coma Recovery Scale-Revised). CONCLUSIONS: This exploratory study suggests that frontoparietal functional disconnections are specifically observed in coma and their structural counterpart provides information about brain injury mechanisms. Multimodal MRI biomarkers of frontoparietal disconnection predict 3-month outcome in our sample. These findings suggest that fronto-parietal disconnection might be particularly relevant for coma outcome prediction and could inspire innovative precision medicine approaches.
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Coma Pós-Traumatismo da Cabeça/patologia , Coma/patologia , Lobo Frontal/patologia , Lobo Parietal/patologia , Adulto , Idoso , Estudos de Casos e Controles , Coma/diagnóstico por imagem , Coma/etiologia , Coma/fisiopatologia , Coma Pós-Traumatismo da Cabeça/diagnóstico por imagem , Coma Pós-Traumatismo da Cabeça/fisiopatologia , Feminino , Lobo Frontal/diagnóstico por imagem , Lobo Frontal/fisiopatologia , Escala de Coma de Glasgow , Parada Cardíaca/complicações , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuroimagem , Lobo Parietal/diagnóstico por imagem , Lobo Parietal/fisiopatologia , Estudos Prospectivos , Adulto JovemRESUMO
BACKGROUND: In sepsis, the endothelial barrier becomes incompetent, with the leaking of plasma into interstitial tissues. VE-cadherin, an adherens junction protein, is the gatekeeper of endothelial cohesion. Kinins, released during sepsis, induce vascular leakage and vasodilation. They act via two G-protein coupled receptors: B1 (B1R) and B2 (B2R). B1R is inducible in the presence of pro-inflammatory cytokines, endotoxins or after tissue injury. It acts at a later stage of sepsis and elicits a sustained inflammatory response. The aim of our study was to investigate the relationships between B1R and VE-cadherin destabilization in vivo in a later phase of sepsis. METHODS: Experimental, prospective study in a university research laboratory. We used a polymicrobial model of septic shock by cecal ligation and puncture in C57BL6 male mice or C57BL6 male mice that received a specific B1R antagonist (R-954). We studied the influence of B1R on sepsis-induced vascular permeability 30 h after surgery for several organs, and VE-cadherin expression in the lung and kidneys by injecting R-954 just before surgery. The 96-h survival was determined in mice without treatment or in animals receiving R-954 as a "prophylactic" regimen (a subcutaneous injection of 200 µg/kg, prior to CLP and 24 h after CLP), or as a "curative" regimen (injection of 100 µg/kg at H6, H24 and H48 post-surgery). RESULTS: B1R inactivation helps to maintain MAP above 65 mmHg but induces different permeability profiles depending on whether or not organ perfusion is autoregulated. In our model, VE-cadherin was destabilized in vivo during septic shock. At a late stage of sepsis, the B1R blockade reduced the VE-cadherin disruption by limiting eNOS activation. The survival rate for mice that received R-954 after sepsis induction was higher than in animals that received an antagonist as a prophylactic treatment. CONCLUSIONS: B1R antagonizing reduced mortality in our model of murine septic shock by limiting the vascular permeability induced by VE-cadherin destabilization through maintenance of the macrohemodynamics, consequently limiting organ dysfunctions.
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Cininas , Sepse , Animais , Masculino , Camundongos , Estudos Prospectivos , Receptor B1 da Bradicinina , Receptor B2 da Bradicinina , Sepse/complicações , Sepse/tratamento farmacológicoRESUMO
Linezolid is an antibiotic used against gram-positive bacteria, including methicillin-resistant Staphylococcus aureus. Its primary adverse effect is haematotoxicity. The objective of this study was to analyse the risk factors for onset of thrombocytopenia in critically ill patients treated with linezolid. This was a retrospective, single-centre study of 72 patients. Platelets were measured from D0 to D20 after the start of treatment. The risk factors for thrombocytopenia were identified using a multivariate logistic regression analysis following a Monte Carlo simulation. Following ROC curve analysis, a baseline platelet count lower than 108 × 109/L and a Cmin higher than 4 mg/L, with respective odds ratios of 117 (95% CI [97-206]) and 3 (95% CI [1.5-6.2]) in the simulated population, were identified as risk factors. Among the source population patients combining these 2 factors, a significantly higher number developed thrombocytopenia (66.7% vs. 33.3%, p = 0.0042). A baseline platelet count lower than 108 × 109/L and a Cmin higher than 4 mg/L are risk factors for the onset of thrombocytopenia in critically ill patients treated with linezolid.
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Antibacterianos/efeitos adversos , Estado Terminal , Linezolida/efeitos adversos , Trombocitopenia/epidemiologia , Trombocitopenia/etiologia , Adulto , Idoso , Antibacterianos/uso terapêutico , Feminino , Humanos , Linezolida/farmacocinética , Linezolida/uso terapêutico , Masculino , Pessoa de Meia-Idade , Método de Monte Carlo , Contagem de Plaquetas , Curva ROC , Medição de Risco , Fatores de Risco , Trombocitopenia/diagnósticoRESUMO
BACKGROUND: Liposomal bupivacaine (Exparel®) is a sustained-release formulation of bupivacaine for use in surgical infiltration anaesthesia. We analysed the histological nerve toxicity and clinical effectiveness of perineural Exparel® alone or with added dexamethasone in a mouse model. METHODS: We assigned 98 mice receiving a perineural sciatic nerve injection into seven groups: sham (n=14, perineural saline), B (n=14, perineural bupivacaine), BDIP (n=14, perineural bupivacaine + intraperitoneal dexamethasone), BDPN (n=14, perineural bupivacaine + perineural dexamethasone), E (n=14, perineural Exparel®), EDIP (n=14, perineural Exparel® + intraperitoneal dexamethasone), and EDPN (n=14, perineural Exparel® + perineural dexamethasone). The duration of thermoalgesic and motor block was evaluated in 49 mice (seven mice randomly selected by group) every 30 min until recovery. Mice were killed for sciatic nerve histological assessment at 14 or 28 days. RESULTS: The median duration of motor block was 90, 120, 120, 120, 180, and 180 min and the duration of thermoalgesic block was 240, 300, 360, 360, 360, and 420 min for groups B, BDIP, BDPN, E, EDIP, and EDPN, respectively. The B group mice showed mild neural inflammation at 14 days and the E group mice showed mild neural inflammation at 28 days. Addition (intraperitoneal or perineural) of dexamethasone reduced neural inflammation induced by bupivacaine, whereas only perineural dexamethasone reduced neural inflammation induced by Exparel®. CONCLUSIONS: Perineural or systemic dexamethasone had a protective effect against the neural inflammation induced by bupivacaine, and perineural dexamethasone attenuated delayed inflammation induced by perineural Exparel®.
Assuntos
Anestésicos Locais/farmacologia , Anti-Inflamatórios/farmacologia , Bupivacaína/farmacologia , Dexametasona/farmacologia , Inflamação/prevenção & controle , Animais , Modelos Animais de Doenças , Interações Medicamentosas , Inflamação/induzido quimicamente , Masculino , Camundongos , Camundongos Endogâmicos C57BL , TempoRESUMO
PURPOSE: Extra Corporeal Membrane Oxygenation (ECMO) is used in cases of severe respiratory and/or circulatory failure over periods of several days to several weeks. Its circuitry requires a closely monitored anticoagulation therapy that is empirically supported by activated clotting time (ACT)-a method often associated with large inter- and intraindividual variability. We aimed to compare the measurement of heparin activity with ACT and the direct measurement of the heparin activity (anti-Xa) in a large ECMO population. METHODS: All patients treated by venoarterial or venovenous ECMO in our intensive care unit between January 2014 and December 2015 were prospectively included. A concomitant measurement of the anti-Xa activity and ACT was performed on the same sample collected twice a day (morning-evening) for unfractionated heparin adaptation with an ACT target range of 180 to 220 seconds. RESULTS: One hundred and nine patients (men 69.7%, median age 54 years) treated with ECMO (70.6% venoarterial) were included. Spearman analysis found no correlation between anti-Xa and ACT (ρ < 0.4) from day 1 and worsened over time. Kappa analysis showed no agreement between the respective target ranges of ACT and anti-Xa. CONCLUSIONS: We demonstrate that concomitant measurement of ACT and anti-Xa activity is irrelevant in ECMO patients. Since ACT is poorly correlated with heparin dosage, anti-Xa activity appears to be a more suitable assay for anticoagulation monitoring.
Assuntos
Anticoagulantes/administração & dosagem , Testes de Coagulação Sanguínea/estatística & dados numéricos , Monitoramento de Medicamentos/estatística & dados numéricos , Oxigenação por Membrana Extracorpórea , Inibidores do Fator Xa/sangue , Coagulação Sanguínea/efeitos dos fármacos , Testes de Coagulação Sanguínea/métodos , Monitoramento de Medicamentos/métodos , Feminino , Heparina/administração & dosagem , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reprodutibilidade dos Testes , Estatísticas não ParamétricasRESUMO
OBJECTIVES: The primary aim of our study was to evaluate and compare the accuracy of ultrasound (US)-guided distal suprascapular nerve (dSSN) and proximal SSN (pSSN) blocks. Secondary aims were to compare the phrenic nerve involvement between groups and to describe the anatomical features of the sensory branches of the dSSN. METHODS: pSSN and dSSN blocks were performed in 14 cadavers (28 shoulders). Ten mL of 0.2% ropivacaine colored with methylene blue was injected under US guidance. Accuracy was determined using SSN staining and the distance between predefined anatomical landmarks and the targeted SSN. The phrenic nerve (PN) was judged to be colored or not. The distribution of the sensory branches that originate from the 14 dSSNs is described. Quantitative data are expressed as median (range). RESULTS: The pSSN was dyed more frequently than the dSSN (13 vs 11, P = 0.59). The targeted SSN was close to the suprascapular notch (1.3 [0-5.2] cm) and the origin of the SSN (1.4 [0.2-4.5] cm) for dSSN and pSSN blocks, respectively (P = 0.62). For dSSN blocks, the most frequent injection site was the supraspinous fossa. Three PNs were marked in pSSN blocks, compared with none in dSSN blocks (P = 0.22). Three sensory branches were identified for all 14 dSSNs: the medial subacromial branch, the lateral subacromial branch, and the posterior glenohumeral branch. CONCLUSIONS: US-guided pSSN and dSSN blocks can be realized with accuracy. A distal approach to the SSN could be an alternative to interscalene brachial plexus block for the management of postoperative pain after shoulder surgery in high-respiratory risk patients.
Assuntos
Nervos Periféricos , Ultrassonografia de Intervenção , Cadáver , Humanos , Injeções Intra-Articulares , UltrassonografiaRESUMO
BACKGROUND: To compare patients hospitalised in the intensive care unit (ICU) after surgery for community-acquired intra-abdominal infection (CA-IAI) and hospital-acquired intra-abdominal infection (HA-IAI) in terms of mortality, severity and complications. METHODS: Retrospective study including all patients admitted to 2 ICUs within 48 h of undergoing surgery for peritonitis. RESULTS: Two hundred twenty-six patients were enrolled during the study period. Patients with CA-IAI had an increased 28-day mortality rate compared to those with HA-IAI (30% vs 15%, respectively (p = 0.009)). At 90 days, the mortality rates were 36.7 and 37.5% in the CA-IAI group and HA-IAI group, respectively, with a similar APACHE II score on admission (median: 21 [15-25] vs. 21 [15-24] respectively, p = 0.63). The patients with HA-IAI had prolonged ICU and hospital stays (median: 17 [7-36] vs. 6[3-12] days, p < 0.001 and 41 [24-66] vs. 17 [7-32] days, p = 0.001), and experienced more complications (reoperation and reintubation) than those with CA-IAI. CONCLUSION: CA-IAI group had higher 28-day mortality rate than HA-IAI group. Mortality was similar at 90 days but those with HA-IAI had a prolonged ICU and hospital stay. In addition, they developed more complications.