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1.
Clin Transplant ; 37(6): e14975, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36964926

RESUMO

PURPOSE: Acute liver failure (ALF) is characterized by hepatic encephalopathy (HE) often due to intracranial hypertension (ICH). The risk/benefit-balance of intraparenchymal pressure catheter monitoring is controversial during ALF. AIMS: Perform an evaluation of transcranial Doppler (TCD) use in patients with ALF listed for emergency liver transplantation. MATERIAL AND METHODS: Single center retrospective cohort study including all patients registered on high emergency LT list between 2012 and 2018. All TCD measurements performed during ICU stay after listing and after LT (when performed) were recorded. TCD was considered abnormal when pulsatility index (PI) was >1.2. RESULTS: Among 106 patients with ALF, forty-seven (44%) had a TCD while on list. They had more severe liver and extrahepatic organ failure. When performed, TCD was abnormal in 51% of patients. These patients more frequently developed ICH events (45% vs. 13%, p = .02) and more frequently required increase in sedative drugs and vasopressors. While 22% of patients with normal TCD spontaneously survived, all of those with abnormal TCD died or were transplanted (p = .02). All transplanted patients who had abnormal exams normalized their TCD within 2 (1-2) days after LT. CONCLUSION: TCD may be a useful non-invasive tool for ICH detection and management, then guide sedation withdrawal.


Assuntos
Hipertensão Intracraniana , Falência Hepática Aguda , Transplante de Fígado , Humanos , Transplante de Fígado/efeitos adversos , Estudos Retrospectivos , Circulação Cerebrovascular , Hipertensão Intracraniana/diagnóstico , Falência Hepática Aguda/etiologia , Falência Hepática Aguda/cirurgia
2.
Anesthesiology ; 134(4): 541-551, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33630043

RESUMO

BACKGROUND: It is speculated that opioid-free anesthesia may provide adequate pain control while reducing postoperative opioid consumption. However, there is currently no evidence to support the speculation. The authors hypothesized that opioid-free balanced anesthetic with dexmedetomidine reduces postoperative opioid-related adverse events compared with balanced anesthetic with remifentanil. METHODS: Patients were randomized to receive a standard balanced anesthetic with either intraoperative remifentanil plus morphine (remifentanil group) or dexmedetomidine (opioid-free group). All patients received intraoperative propofol, desflurane, dexamethasone, lidocaine infusion, ketamine infusion, neuromuscular blockade, and postoperative lidocaine infusion, paracetamol, nefopam, and patient-controlled morphine. The primary outcome was a composite of postoperative opioid-related adverse events (hypoxemia, ileus, or cognitive dysfunction) within the first 48 h after extubation. The main secondary outcomes were episodes of postoperative pain, opioid consumption, and postoperative nausea and vomiting. RESULTS: The study was stopped prematurely because of five cases of severe bradycardia in the dexmedetomidine group. The primary composite outcome occurred in 122 of 156 (78%) dexmedetomidine group patients compared with 105 of 156 (67%) in the remifentanil group (relative risk, 1.16; 95% CI, 1.01 to 1.33; P = 0.031). Hypoxemia occurred 110 of 152 (72%) of dexmedetomidine group and 94 of 155 (61%) of remifentanil group patients (relative risk, 1.19; 95% CI, 1.02 to 1.40; P = 0.030). There were no differences in ileus or cognitive dysfunction. Cumulative 0 to 48 h postoperative morphine consumption (11 mg [5 to 21] versus 6 mg [0 to 17]) and postoperative nausea and vomiting (58 of 157 [37%] versus 37 of 157 [24%]; relative risk, 0.64; 95% CI, 0.45 to 0.90) were both less in the dexmedetomidine group, whereas measures of analgesia were similar in both groups. Dexmedetomidine patients had more delayed extubation and prolonged postanesthesia care unit stay. CONCLUSIONS: This trial refuted the hypothesis that balanced opioid-free anesthesia with dexmedetomidine, compared with remifentanil, would result in fewer postoperative opioid-related adverse events. Conversely, it did result in a greater incidence of serious adverse events, especially hypoxemia and bradycardia.


Assuntos
Analgésicos não Narcóticos/uso terapêutico , Analgésicos Opioides/uso terapêutico , Anestesia Balanceada/métodos , Dexmedetomidina/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Remifentanil/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Método Simples-Cego , Resultado do Tratamento
3.
Brain ; 142(12): 3806-3833, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31665242

RESUMO

Microglia of the developing brain have unique functional properties but how their activation states are regulated is poorly understood. Inflammatory activation of microglia in the still-developing brain of preterm-born infants is associated with permanent neurological sequelae in 9 million infants every year. Investigating the regulators of microglial activation in the developing brain across models of neuroinflammation-mediated injury (mouse, zebrafish) and primary human and mouse microglia we found using analysis of genes and proteins that a reduction in Wnt/ß-catenin signalling is necessary and sufficient to drive a microglial phenotype causing hypomyelination. We validated in a cohort of preterm-born infants that genomic variation in the Wnt pathway is associated with the levels of connectivity found in their brains. Using a Wnt agonist delivered by a blood-brain barrier penetrant microglia-specific targeting nanocarrier we prevented in our animal model the pro-inflammatory microglial activation, white matter injury and behavioural deficits. Collectively, these data validate that the Wnt pathway regulates microglial activation, is critical in the evolution of an important form of human brain injury and is a viable therapeutic target.


Assuntos
Encéfalo/metabolismo , Inflamação/metabolismo , Microglia/metabolismo , Via de Sinalização Wnt/fisiologia , Animais , Animais Geneticamente Modificados , Barreira Hematoencefálica/metabolismo , Células Cultivadas , Biologia Computacional , Humanos , Camundongos , Peixe-Zebra
5.
Brain Behav Immun ; 63: 197-209, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27818218

RESUMO

The cognitive and behavioural deficits caused by traumatic brain injury (TBI) to the immature brain are more severe and persistent than TBI in the mature brain. Understanding this developmental sensitivity is critical as children under four years of age sustain TBI more frequently than any other age group. Microglia (MG), resident immune cells of the brain that mediate neuroinflammation, are activated following TBI in the immature brain. However, the type and temporal profile of this activation and the consequences of altering it are still largely unknown. In a mouse model of closed head weight drop paediatric brain trauma, we characterized i) the temporal course of total cortical neuroinflammation and the phenotype of ex vivo isolated CD11B-positive microglia/macrophage (MG/MΦ) using a battery of 32 markers, and ii) neuropathological outcome 1 and 5days post-injury. We also assessed the effects of targeting MG/MΦ activation directly, using minocycline a prototypical microglial activation antagonist, on these processes and outcome. TBI induced a moderate increase in both pro- and anti-inflammatory cytokines/chemokines in the ipsilateral hemisphere. Isolated cortical MG/MΦ expressed increased levels of markers of endogenous reparatory/regenerative and immunomodulatory phenotypes compared with shams. Blocking MG/MΦ activation with minocycline at the time of injury and 1 and 2days post-injury had only transient protective effects, reducing ventricular dilatation and cell death 1day post-injury but having no effect on injury severity at 5days. This study demonstrates that, unlike in adults, the role of MG/MΦ in injury mechanisms following TBI in the immature brain may not be negative. An improved understanding of MG/MΦ function in paediatric TBI could support translational efforts to design therapeutic interventions.


Assuntos
Lesões Encefálicas Traumáticas/metabolismo , Ativação de Macrófagos/fisiologia , Microglia/metabolismo , Animais , Encéfalo/metabolismo , Lesões Encefálicas/imunologia , Lesões Encefálicas/metabolismo , Lesões Encefálicas Traumáticas/imunologia , Quimiocinas/imunologia , Quimiocinas/metabolismo , Citocinas/imunologia , Citocinas/metabolismo , Modelos Animais de Doenças , Ativação de Macrófagos/efeitos dos fármacos , Ativação de Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Minociclina/farmacologia
6.
Dev Med Child Neurol ; 57 Suppl 3: 17-28, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25800488

RESUMO

Perinatal insults are a leading cause of infant mortality and amongst survivors are frequently associated with neurocognitive impairment, cerebral palsy (CP), and seizure disorders. The events leading to perinatal brain injury are multifactorial. This review describes how one subinjurious factor affecting the brain sensitizes it to a second injurious factor, causing an exacerbated injurious cascade. We will review the clinical and experimental evidence, including observations of high rates of maternal and fetal infections in term-born infants with neonatal encephalopathy and cerebral palsy. In addition, we will discuss preclinical evidence for the sensitizing effects of inflammation on injuries, such as hypoxia-ischaemia, our current understanding of the mechanisms underpinning the sensitization process, and the possibility for neuroprotection.


Assuntos
Lesões Encefálicas/etiologia , Inflamação/complicações , Animais , Encéfalo/anormalidades , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Lactente , Recém-Nascido , Troca Materno-Fetal , Gravidez
7.
Biochem Soc Trans ; 42(2): 557-63, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24646278

RESUMO

Epidemiological studies have shown a strong association between perinatal infection/inflammation and brain damage in preterm infants and/or neurological handicap in survivors. Experimental studies have shown a causal effect of infection/inflammation on perinatal brain damage. Infection including inflammatory factors can disrupt programmes of brain development and, in particular, induce death and/or blockade of oligodendrocyte maturation, leading to myelin defects. Alternatively, in the so-called multiple-hit hypothesis, infection/inflammation can act as predisposing factors, making the brain more susceptible to a second stress (sensitization process), such as hypoxic-ischaemic or excitotoxic insults. Epidemiological data also suggest that perinatal exposure to inflammatory factors could predispose to long-term diseases including psychiatric disorders.


Assuntos
Encéfalo/patologia , Paralisia Cerebral/epidemiologia , Paralisia Cerebral/imunologia , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Inflamação/epidemiologia , Inflamação/imunologia , Gravidez
8.
Ann Neurol ; 73(5): 667-78, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23494575

RESUMO

OBJECTIVE: The concept of inflammation-induced sensitization is emerging in the field of perinatal brain injury, stroke, Alzheimer disease, and multiple sclerosis. However, mechanisms underpinning this process remain unidentified. METHODS: We combined in vivo systemic lipopolysaccharide-induced or interleukin (IL)-1ß-induced sensitization of neonatal and adult rodent cortical neurons to excitotoxic neurodegeneration with in vitro IL-1ß sensitization of human and rodent neurons to excitotoxic neurodegeneration. Within these inflammation-induced sensitization models, we assessed metabotropic glutamate receptors (mGluR) signaling and regulation. RESULTS: We demonstrate for the first time that group I mGluRs mediate inflammation-induced sensitization to neuronal excitotoxicity in neonatal and adult neurons across species. Inflammation-induced G protein-coupled receptor kinase 2 (GRK2) downregulation and genetic deletion of GRK2 mimicked the sensitizing effect of inflammation on excitotoxic neurodegeneration. Thus, we identify GRK2 as a potential molecular link between inflammation and mGluR-mediated sensitization. INTERPRETATION: Collectively, our findings indicate that inflammation-induced sensitization is universal across species and ages and that group I mGluRs and GRK2 represent new avenues for neuroprotection in perinatal and adult neurological disorders.


Assuntos
Córtex Cerebral/metabolismo , Quinase 2 de Receptor Acoplado a Proteína G/metabolismo , Inflamação/complicações , Doenças Neurodegenerativas/metabolismo , Receptores de Glutamato Metabotrópico/metabolismo , Análise de Variância , Animais , Animais Recém-Nascidos , Cálcio/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/genética , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/patologia , Citocinas/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Agonistas de Aminoácidos Excitatórios/toxicidade , Feminino , Quinase 2 de Receptor Acoplado a Proteína G/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/genética , Proteína Glial Fibrilar Ácida/genética , Proteína Glial Fibrilar Ácida/metabolismo , Humanos , Ácido Ibotênico/toxicidade , Inflamação/induzido quimicamente , Interleucina-1beta/toxicidade , Lipopolissacarídeos/toxicidade , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Doenças Neurodegenerativas/etiologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Síndromes Neurotóxicas/etiologia , Síndromes Neurotóxicas/metabolismo , Síndromes Neurotóxicas/patologia , Fosfolipase C beta/metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Ratos , Receptores de Glutamato Metabotrópico/genética
9.
Anesthesiology ; 120(3): 590-600, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23903022

RESUMO

BACKGROUND: The optimal dose of tranexamic acid (TA) is still an issue. The authors compared two doses of TA during cardiac surgery in a multicenter, double-blinded, randomized study. METHODS: Patients were stratified according to transfusion risk, then randomized to two TA doses: 10 mg/kg bolus followed by 1 mg·kg·h infusion (low dose) until the end of surgery or 30 mg/kg bolus followed by 16 mg·kg·h infusion (high dose). The primary endpoint was the incidence of blood product transfusion up to day 7. Secondary ones were incidences of transfusion for each type of blood product and amounts transfused, blood loss, repeat surgery, TA-related adverse events, and mortality. RESULTS: The low-dose group comprised 284 patients and the high-dose one 285. The primary endpoint was not significantly different between TA doses (63% for low dose vs. 60% for high dose; P = 0.3). With the high dose, a lower incidence of frozen plasma (18 vs. 26%; P = 0.03) and platelet concentrate (15 vs. 23%; P = 0.02) transfusions, lower amounts of blood products (2.5 ± 0.38 vs. 4.1 ± 0.39; P = 0.02), fresh frozen plasma (0.49 ± 0.14 vs.1.07 ± 0.14; P = 0.02), and platelet concentrates transfused (0.50 ± 0.15 vs. 1.13 ± 0.15; P = 0.02), lower blood loss (590 ± 50.4 vs. 820 ± 50.7; P = 0.01), and less repeat surgery (2.5 vs. 6%; P = 0.01) were observed. These results are more marked in patients with a high risk for transfusion. CONCLUSIONS: A high dose of TA does not reduce incidence of blood product transfusion up to day 7, but is more effective than a low dose to decrease transfusion needs, blood loss, and repeat surgery.


Assuntos
Antifibrinolíticos/farmacologia , Transfusão de Sangue/estatística & dados numéricos , Procedimentos Cirúrgicos Cardíacos , Ponte Cardiopulmonar , Ácido Tranexâmico/farmacologia , Idoso , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Plaquetas , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Masculino , Plasma , Transfusão de Plaquetas/estatística & dados numéricos , Retratamento , Resultado do Tratamento
11.
JHEP Rep ; 6(6): 101051, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38699073

RESUMO

Background & Aims: Major bleeding events during orthotopic liver transplantation (OLT) are associated with poor outcomes. The proportion of this risk related to portal hypertension is unclear. Hepatic venous pressure gradient (HVPG) is the gold standard for estimating portal hypertension. The aim of this study was to analyze the ability of HVPG to predict intraoperative major bleeding events during OLT in patients with cirrhosis. Methods: We retrospectively analyzed a prospective database including all patients with cirrhosis who underwent OLT between 2010 and 2020 and had liver and right heart catheterizations as part of their pre-transplant assessment. The primary endpoint was the occurrence of an intraoperative major bleeding event. Results: The 468 included patients had a median HVPG of 17 mmHg [interquartile range, 13-22] and a median MELD on the day of OLT of 16 [11-24]. Intraoperative red blood cell transfusion was required in 72% of the patients (median 2 units transfused), with a median blood loss of 1,000 ml [575-1,500]. Major intraoperative bleeding occurred in 156 patients (33%) and was associated with HVPG, preoperative hemoglobin level, severity of cirrhosis at the time of OLT (MELD score, ascites, encephalopathy), hemostasis impairment (thrombocytopenia, lower fibrinogen levels), and complications of cirrhosis (sepsis, acute-on-chronic liver failure). By multivariable regression analysis with backward elimination, HVPG, preoperative hemoglobin level, MELD score, and tranexamic acid infusion were associated with the primary endpoint. Three categories of patients were identified according to HVPG: low-risk (HVPG <16 mmHg), high-risk (HVGP ≥16 mmHg), and very high-risk (HVPG ≥20 mmHg). Conclusions: HVPG predicted major bleeding events in patients with cirrhosis undergoing OLT. Including HVPG as part of pre-transplant assessment might enable better anticipation of the intraoperative course. Impact and implications: Major bleeding events during orthotopic liver transplantation (OLT) are associated with poor outcomes but the proportion of this risk related to portal hypertension is unclear. Our work shows that hepatic venous pressure gradient (HVPG), the gold standard for estimating portal hypertension, is a strong predictor of major bleeding events and blood loss volume in patients with cirrhosis undergoing OLT. Three groups of patients can be identified according to their risk of major bleeding events: low-risk patients with HVPG <16 mmHg, high-risk patients with HVPG ≥16 mmHg, and very high-risk patients with HVPG ≥20 mmHg. HVPG could be systematically included in the pre-transplant assessment to anticipate intraoperative course and tailor patient management.

12.
Eur J Trauma Emerg Surg ; 49(3): 1227-1234, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35169869

RESUMO

PURPOSES: External ventricular drainage (EVD) is frequently used to control raised intracranial pressure after traumatic brain injury. However, the available evidence about its effectiveness in this context is limited. The aim of this study is to evaluate the effectiveness of EVD to control intracranial pressure and to identify the clinical and radiological factors associated with its success. METHODS: For this retrospective cohort study conducted in a Level 1 traumacenter in Paris area between May 2011 and March 2019, all patients with intracranial hypertension and treated with EVD were included. EVD success was defined as an efficient and continuous control of intracranial hypertension avoiding the use of third tier therapies (therapeutic hypothermia, decompressive craniectomy, and barbiturate coma) or avoiding a decision to withdraw life sustaining treatment due to both refractory intracranial hypertension and severity of brain injury lesions. RESULTS: 83 patients with EVD were included. EVD was successful in 33 patients (40%). Thirty-two patients (39%) required a decompressive craniectomy, eight patients (9%) received barbiturate coma. In ten cases (12%) refractory intracranial hypertension prompted a protocolized withdrawal of care. Complications occurred in nine patients (11%) (three cases of ventriculitis, six cases of catheter occlusion). Multivariate analysis identified no independent factors associated with EVD success. CONCLUSION: In a protocol-based management for traumatic brain injury, EVD allowed intracranial pressure control and avoided third tier therapeutic measures in 40% of cases with a favorable risk-benefit ratio.


Assuntos
Lesões Encefálicas Traumáticas , Drenagem , Hipertensão Intracraniana , Humanos , Barbitúricos , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/cirurgia , Coma/complicações , Hipertensão Intracraniana/etiologia , Hipertensão Intracraniana/cirurgia , Estudos Retrospectivos
13.
Eur J Trauma Emerg Surg ; 48(4): 3131-3140, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35064284

RESUMO

PURPOSE: Blunt cerebrovascular injuries (BCVI) are a rare but serious complication after trauma. Among patients with BCVI, neurological status is altered in 30% of cases and the prognosis seems to be associated with ischemic complications. The aim of this study was to assess the long-term outcome of BCVI-associated ischemic events. METHODS: This retrospective cohort study (2011-2017) included all patients admitted for severe trauma with identified BCVI in two level-1 trauma centers. Patients were considered to have a poor neurological outcome with a GOS-E between 2 and 5 and a good neurological outcome with GOS-E between 6 and 8. A multivariate logistic regression identified risk factors for poor neurological outcome at 1 year. RESULTS: Of the 6,294 patients admitted in both trauma centers between 2011 and 2017, 81 patients presenting BCVI were identified (incidence of 1.3%). The median age was 35 years (24-44) with a median Injury Severity Score of 28 (17-41). 29 patients (50%) had a good neurological prognosis, while 25 patients (43%) had a poor neurological prognosis at 1 year. Ischemic stroke occurred in 11 patients (13.6%) within a median time of 2 days (2-2.5). No ischemic stroke occurred in the first year after ICU discharge in both groups. In our study, good prognosis at 1 year was not associated with ischemic complications [3 (10) vs 3 (12) p = 1]. CONCLUSION: Ischemic complications after BCVI are rare, occur within the first week and do not seem to impact independently the 1-year neurological prognosis.


Assuntos
Traumatismo Cerebrovascular , Acidente Vascular Cerebral , Ferimentos não Penetrantes , Adulto , Traumatismo Cerebrovascular/complicações , Traumatismo Cerebrovascular/epidemiologia , Traumatismo Cerebrovascular/terapia , Humanos , Escala de Gravidade do Ferimento , Estudos Retrospectivos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/epidemiologia , Resultado do Tratamento , Ferimentos não Penetrantes/complicações , Ferimentos não Penetrantes/epidemiologia , Ferimentos não Penetrantes/terapia
14.
Transplantation ; 106(4): 781-791, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-34172644

RESUMO

BACKGROUND: Acute kidney injury (AKI) is a common complication after liver transplantation (LT), but the specific impact of rapidly resolving AKI is not elucidated. This study investigates the factors associated with early recovery from AKI and its association with post-LT outcomes. METHODS: Retrospective analysis of 441 liver transplant recipients with end-stage liver disease without pretransplant renal impairment. AKI was defined according to Kidney Disease Improving Global Outcomes criteria and early renal recovery by its disappearance within 7 d post-LT. RESULTS: One hundred forty-six patients (32%) developed a post-LT AKI, of whom 99 (69%) recovered early and 45 (31%) did not. Factors associated with early recovery were Kidney Disease Improving Global Outcomes stage 1 (odds ratio [OR],14.11; 95% confidence interval [CI], 5.59-40.22; P < 0.0001), minimum prothrombin time >50 % (OR, 4.50; 95% CI, 1.67-13.46; P = 0.003) and aspartate aminotransferase peak value <1000 U/L (OR, 4.07; 95% CI, 1.64-10.75; P = 0.002) within 48 h post-LT. Patients with early recovery had a renal prognosis similar to that of patients without AKI with no difference in estimated glomerular filtration rate between day 7 and 1 y. Their relative risk of developing chronic kidney disease was 0.88 (95% CI, 0.55-1.41; P = 0.6) with survival identical to patients without AKI and better than patients without early recovery (P < 0.0001). CONCLUSIONS: Most patients with post-LT AKI recover early and have a similar renal prognosis and survival to those without post-LT AKI. Factors associated with early renal recovery are related to the stage of AKI, the extent of liver injury, and the early graft function. Patients at risk of not recovering may benefit the most from perioperative protective strategies, particularly those aimed at minimizing the adverse effects of calcineurin inhibitors.


Assuntos
Injúria Renal Aguda , Doença Hepática Terminal , Transplante de Fígado , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/etiologia , Doença Hepática Terminal/complicações , Taxa de Filtração Glomerular , Humanos , Transplante de Fígado/efeitos adversos , Prognóstico , Estudos Retrospectivos , Fatores de Risco
15.
BMJ Open ; 11(12): e053908, 2021 12 24.
Artigo em Inglês | MEDLINE | ID: mdl-34952881

RESUMO

INTRODUCTION: Postoperative delirium (POD) is one of the most frequent complication after surgery in elderly patients, and is associated with increased morbidity and mortality, prolonged length of stay, cognitive and functional decline leading to loss of autonomy, and important additional healthcare costs. Perioperative inflammatory stress is a key element in POD genesis. Melatonin exhibits antioxidative and immune-modulatory proprieties that are promising concerning delirium prevention, but in perioperative context literature are scarce and conflicting. We hypothesise that perioperative melatonin can reduce the incidence of POD. METHODS AND ANALYSIS: The DELIRLESS trial is a prospective, national multicentric, phase III, superiority, comparative randomised (1:1) double-blind clinical trial. Among patients aged 70 or older, hospitalised and scheduled for surgery of a severe fracture of a lower limb, 718 will be randomly allocated to receive either melatonin 4 mg per os or placebo, every night from anaesthesiologist preoperative consultation and up to 5 days after surgery. The primary outcome is POD incidence measured by either the French validated translation of the Confusion Assessment Method (CAM) score for patients hospitalised in surgery, or CAM-ICU score for patients hospitalised in ICU (Intensive Care Unit). Daily delirium assessment will take place during 10 days after surgery, or until the end of hospital stay if it is shorter. POD cumulative incidence function will be compared at day 10 between the two randomised arms in a competing risks framework, using the Fine and Grey model with death as a competing risk of delirium. ETHICS AND DISSEMINATION: The DELIRLESS trial has been approved by an independent ethics committee the Comité de Protection des Personnes (CPP) Sud-Est (ref CPP2020-18-99 2019-003210-14) for all study centres. Participant recruitment begins in December 2020. Results will be published in international peer-reviewed medical journals. TRIAL REGISTRATION NUMBER: NCT04335968, first posted 7 April 2020. PROTOCOL VERSION IDENTIFIER: N°3-0, 3 May 2021.


Assuntos
Delírio , Fraturas do Quadril , Melatonina , Idoso , Delírio/epidemiologia , Delírio/etiologia , Delírio/prevenção & controle , Método Duplo-Cego , Fraturas do Quadril/complicações , Humanos , Extremidade Inferior/cirurgia , Melatonina/uso terapêutico , Estudos Multicêntricos como Assunto , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto
16.
Anaesth Crit Care Pain Med ; 40(3): 100874, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33946037

RESUMO

We report data regarding three countries with similar healthcare systems which had three different vaccinal strategies between 1st of January and 10th of April 2021: rapid full vaccination (Israel), rapid first-dose vaccination (United Kingdom) and a delayed vaccination strategy (France).


Assuntos
Vacinas contra COVID-19/administração & dosagem , COVID-19/prevenção & controle , Hospitalização/estatística & dados numéricos , Programas de Imunização/estatística & dados numéricos , Brasil , COVID-19/virologia , França , Humanos , Programas de Imunização/métodos , Esquemas de Imunização , Israel , SARS-CoV-2/imunologia , África do Sul , Reino Unido
18.
Anesth Analg ; 108(2): 601-8, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19151295

RESUMO

BACKGROUND: The neuroprotective efficacy of anesthetics observed in experimental models remains unproven in the clinical setting. The nonreceptor tyrosine kinase focal adhesion kinase (FAK) has been suggested to be involved in the neuroprotective effect of anesthetics observed experimentally. In the present work, we investigated whether FAK and the duration of ischemia play a role in the preconditioning effect of sevoflurane on brain tissue. METHODS: Rat acute hippocampal slices were subjected to oxygen and glucose deprivation (OGD) challenge during increasing periods of time (10, 20, 30, 45, 50, and 60 min) followed by 1 h reperfusion. A preconditioning sevoflurane concentration (10(-4) M, 1 h) was applied 3 h before initiation of OGD. Protein expression of FAK and cleaved caspase 3 (a marker of activation of the apoptotic cascade) was measured by immunoblotting. Cell death was assessed by propidium iodide (PI) fluorescence. RESULTS: Both PI fluorescence and expression of cleaved caspase 3 significantly increased with duration of ischemia until reaching a ceiling effect for durations of ischemia longer than 30 min. Sevoflurane (10(-4) M) increased FAK expression and markedly reduced the increase in PI fluorescence and cleaved caspase 3 expression for periods of ischemia of 10, 20, and 30 min. In contrast, the protective effect was no longer observed for periods of ischemia longer than 30 min. 4-amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazolo[3,4-d] pyrimidine (PP2, 10(-5) M, an inhibitor of src tyrosine kinases) application 60 min before and throughout that of sevoflurane significantly reduced the neuroprotective effect of sevoflurane on both caspase 3 expression and PI fluorescence. CONCLUSION: In the OGD rat acute hippocampal slice, the preconditioning effect of a clinically relevant concentration of sevoflurane was very likely to involve FAK and was observed only for periods of ischemia

Assuntos
Anestésicos Inalatórios/farmacologia , Isquemia Encefálica/fisiopatologia , Proteína-Tirosina Quinases de Adesão Focal/fisiologia , Glucose/deficiência , Hipocampo/fisiopatologia , Hipóxia Encefálica/fisiopatologia , Éteres Metílicos/farmacologia , Actinas/metabolismo , Animais , Gasometria , Isquemia Encefálica/enzimologia , Caspase 3/metabolismo , Morte Celular/efeitos dos fármacos , Circulação Cerebrovascular/efeitos dos fármacos , Circulação Cerebrovascular/fisiologia , Hipocampo/irrigação sanguínea , Hipocampo/enzimologia , Concentração de Íons de Hidrogênio , Hipóxia Encefálica/enzimologia , Masculino , Fármacos Neuroprotetores , Fosforilação , Ratos , Ratos Sprague-Dawley , Sevoflurano , Transdução de Sinais/fisiologia
19.
Paediatr Anaesth ; 19(12): 1199-206, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19863734

RESUMO

INTRODUCTION: Central venous catheter placement is technically difficult in pediatric population especially in the younger patients. Ultrasound prelocation and/or guidance (UPG) of internal jugular vein (IJV) access has been shown to decrease failure rate and complications related to this invasive procedure. The goal of the present study was to perform a systematic review of the advantages of UPG over anatomical landmarks (AL) during IJV access in children and infants. MATERIAL AND METHODS: A comprehensive literature search was conducted to identify clinical trials that focused on the comparison of UPG to AL techniques during IJV access in children and infants. Two reviewers independently assessed each study to meet inclusion criteria and extracted data. Data from each trial were combined to calculate the pooled odds ratio (OR) or the mean differences (MD), and their 95% confidence intervals [CI 95%]. I(2) statistics were used to assess statistics heterogeneity and to guide the use of fixed or random effect for computation of overall effects. Subgroup analysis was used to clarify the effects of the techniques used (prelocation or guidance) or the experience of practitioners. RESULTS: Literature found five articles. Most of the patients were cardiac surgery patients. In comparison with AL, UPG had no effect on IJV access failure rate (OR = 0.28 [0.05, 1.47], I(2) = 75%, P = 0.003), the rate of carotid artery puncture (OR = 0.32 [0.06, 1.62], I(2) = 68%, P = 0.01), haematoma, haemothorax, or pneumothorax occurrence (OR = 0.40 [0.14, 1.13], I(2) = 17%, P = 0.30, OR = 0.72, OR = 0.81 [0.18, 3.73], I(2) = 0%, P = 0.94, respectively) and time to IJV access and haemothorax/pneumothorax occurrence. Subgroup analysis found an efficacy of ultrasound when used by novice operators or during intraoperative use. DISCUSSION: This current meta-analysis does not found the utility of ultrasound during IJV access in children and infants in increasing the success rate and in decreasing complications.


Assuntos
Cateterismo Venoso Central , Veias Jugulares/diagnóstico por imagem , Ultrassonografia de Intervenção , Lesões das Artérias Carótidas/etiologia , Cateterismo Venoso Central/efeitos adversos , Cateterismo Venoso Central/instrumentação , Cateterismo Venoso Central/métodos , Criança , Pré-Escolar , Hematoma/etiologia , Humanos , Lactente , Recém-Nascido , Veias Jugulares/anatomia & histologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
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