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1.
Front Neurol ; 15: 1387505, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38533411

RESUMO

Bickerstaff brainstem encephalitis (BBE) is a rare autoimmune disease characterized by the subacute onset of bilateral external ophthalmoplegia, ataxia, and decreased level of consciousness. BBE is part of a group of rare autoimmune diseases in children that can affect the nervous system at any level. The onset of neurological deficits is often sudden and nonspecific. The diagnosis is based on clinical findings and abnormal findings on cerebrospinal fluid (CSF), electroencephalography (EEG), electromyography (EMG), and magnetic resonance imaging (MRI). BBE is associated with the presence of the antiganglioside antibody, anti-GQ1b and anti-GM1. Intravenous immunoglobulin (IVIg) and plasma exchange are often used as treatments for these patients. We conducted a review on clinical presentation, diagnosis, treatment and outcome of reported cases of BBE. 74 cases are reported in the literature from the first cases described in 1951 to today. The prevalence is unknown while the incidence is higher in males. In 50% of cases, BBE occurs following respiratory or gastrointestinal tract infections. The most frequent initial symptoms were consciousness disturbance, headache, vomiting, diplopia, gait disturbance, dysarthria and fever. During illness course, almost all the patients developed consciousness disturbance, external ophthalmoplegia, and ataxia. Lumbar puncture showed pleocytosis or cytoalbuminological dissociation. Abnormal EEG and MRI studies revealed abnormalities in most cases. Anti-GQ1b antibodies were detected in more than half of the patients; anti-GM1 antibodies were detected in almost 40% of patients. Treatment guidelines are missing. In our analysis, steroids and IVIg were administered alone or in combination; as last option, plasmapheresis was used. BBE has a good prognosis and recovery in childhood is faster than in adulthood; 70% of patients reported no sequelae in our analysis. Future studies need to investigate pathogenesis and possible triggers, and therapeutic possibilities.

2.
Minerva Anestesiol ; 90(3): 135-143, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-37987991

RESUMO

BACKGROUND: The growing number of elderly patients in hospitals is a challenge for healthcare systems. The main objective is to measure the postoperative change in the cognitive status at hospital discharge and one year after discharge in elderly patients undergoing planned or deferrable surgery. METHODS: We planned a prospective longitudinal study, single-center study: secondary care level hospital, enrolment from September 2018 to May 2019. We enroll elderly patients, aged above life expectancy in Italy, who underwent planned or deferrable surgery (men over 80.5 years old, women over 85.0 years old). In six months, we enrolled 76 eligible patients. We collected the scores of the clinical impairment scales Charlson Index, Barthel Index, and Six-Item Cognitive Impairment Test (6CIT). The primary endpoint was the postoperative worsening of the cognitive status at one-year follow-up. Secondary endpoints aimed to describe postoperative disabilities and complications, to investigate possible risk factors for cognitive worsening, and to measure the role of anesthesia in cognitive changes. RESULTS: We recorded an increased rate of pathological 6CIT values during the hospitalization period, rising from 39.47% to 55.26% (McNemar test, P=0.007), and this rate was still increased at 55.56% (P=0.021) one year after discharge. Anesthesia did not show any significant harmful effect on cognitive status. The preoperative hemoglobin value seems to be a risk factor for cognitive status and one-year mortality. CONCLUSIONS: Elderly patients had a significantly worse 6CIT value after planned surgery, which may derive in part from age and in part from hospitalization. It is difficult to determine if general anesthesia alone has no harmful effects on cognitive performance in patients at discharge and one year later. Further data are necessary.


Assuntos
Cognição , Hospitalização , Idoso , Masculino , Humanos , Feminino , Idoso de 80 Anos ou mais , Estudos Prospectivos , Estudos Longitudinais , Expectativa de Vida , Complicações Pós-Operatórias
3.
Crit Care ; 27(1): 221, 2023 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-37280579

RESUMO

OBJECTIVE: To describe the potential effects of ventilatory strategies on the outcome of acute brain-injured patients undergoing invasive mechanical ventilation. DESIGN: Systematic review with an individual data meta-analysis. SETTING: Observational and interventional (before/after) studies published up to August 22nd, 2022, were considered for inclusion. We investigated the effects of low tidal volume Vt < 8 ml/Kg of IBW versus Vt > = 8 ml/Kg of IBW, positive end-expiratory pressure (PEEP) < or > = 5 cmH2O and protective ventilation (association of both) on relevant clinical outcomes. POPULATION: Patients with acute brain injury (trauma or haemorrhagic stroke) with invasive mechanical ventilation for ≥ 24 h. MAIN OUTCOME MEASURES: The primary outcome was mortality at 28 days or in-hospital mortality. Secondary outcomes were the incidence of acute respiratory distress syndrome (ARDS), the duration of mechanical ventilation and the partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio. RESULTS: The meta-analysis included eight studies with a total of 5639 patients. There was no difference in mortality between low and high tidal volume [Odds Ratio, OR 0.88 (95%Confidence Interval, CI 0.74 to 1.05), p = 0.16, I2 = 20%], low and moderate to high PEEP [OR 0.8 (95% CI 0.59 to 1.07), p = 0.13, I2 = 80%] or protective and non-protective ventilation [OR 1.03 (95% CI 0.93 to 1.15), p = 0.6, I2 = 11]. Low tidal volume [OR 0.74 (95% CI 0.45 to 1.21, p = 0.23, I2 = 88%], moderate PEEP [OR 0.98 (95% CI 0.76 to 1.26), p = 0.9, I2 = 21%] or protective ventilation [OR 1.22 (95% CI 0.94 to 1.58), p = 0.13, I2 = 22%] did not affect the incidence of acute respiratory distress syndrome. Protective ventilation improved the PaO2/FiO2 ratio in the first five days of mechanical ventilation (p < 0.01). CONCLUSIONS: Low tidal volume, moderate to high PEEP, or protective ventilation were not associated with mortality and lower incidence of ARDS in patients with acute brain injury undergoing invasive mechanical ventilation. However, protective ventilation improved oxygenation and could be safely considered in this setting. The exact role of ventilatory management on the outcome of patients with a severe brain injury needs to be more accurately delineated.


Assuntos
Lesões Encefálicas , Síndrome do Desconforto Respiratório , Humanos , Respiração Artificial , Volume de Ventilação Pulmonar , Síndrome do Desconforto Respiratório/terapia , Oxigênio , Lesões Encefálicas/terapia
4.
BMC Neurol ; 23(1): 228, 2023 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-37312033

RESUMO

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.


Assuntos
Doenças Cardiovasculares , Hemorragia Subaracnóidea , Feminino , Gravidez , Humanos , Hemorragia Subaracnóidea/complicações , Estudos Retrospectivos , Escala de Resultado de Glasgow , Hospitalização
5.
Neurol Sci ; 44(6): 2061-2069, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36705784

RESUMO

BACKGROUND: Neurological outcome after endovascular treatment (EVT) of acute ischemic stroke (AIS) may depend on both patient-specific and procedural factors. We hypothesized that altered systemic homeostasis might be frequent and affect outcome in these patients. The aim of this study was to analyze secondary insults during EVT of AIS and its association with outcome and anesthesiologic regimen. METHODS: This was a single-center prospective observational study on patients undergoing EVT for AIS under local anesthesia (LA), conscious sedation (CS), or general anesthesia (GA). Altered systemic parameters were recorded and quantified as secondary insults. The primary endpoint was to evaluate number, duration, and severity of secondary insults during EVT. Secondary endpoints were to analyze association of insults with modified Rankin Scale at 90 days and anesthesiologic regimen. RESULTS AND CONCLUSIONS: One hundred twenty patients were enrolled. Overall, 78% of patients experienced at least one episode of hypotension, 21% hypertension, 54% hypoxemia, 16% bradycardia, and 13% tachycardia. In patients monitored with capnometry, 70% experienced hypocapnia and 21% hypercapnia. LA was selected in 24 patients, CS in 84, and GA in 12. Hypotension insult was more frequent during GA than LA and CS (p = 0.0307), but intraprocedural blood pressure variation was higher during CS (p = 0.0357). Hypoxemia was more frequent during CS (p = 0.0087). Proportion of hypotension duration was higher in unfavorable outcome but secondary insults did not remain in the final model of multivariable analysis. Secondary insults occurred frequently during EVT for AIS but the main predictors of outcome were age, NIHSS at admission, and prompt and successful recanalization.


Assuntos
Isquemia Encefálica , Procedimentos Endovasculares , Hipotensão , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , AVC Isquêmico/etiologia , Isquemia Encefálica/tratamento farmacológico , Resultado do Tratamento , Acidente Vascular Cerebral/cirurgia , Acidente Vascular Cerebral/tratamento farmacológico , Anestesia Geral/efeitos adversos , Anestesia Geral/métodos , Trombectomia/efeitos adversos , Hipotensão/etiologia , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/métodos
6.
Thorac Surg Clin ; 32(2): 143-151, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35512933

RESUMO

The use of donor management protocols has significantly improved recovery rates; however, the inherent instability of lungs after death results in low utilization rates of potential donor lungs. Donor lungs are susceptible to direct trauma, aspiration, neurogenic edema, ventilator-associated barotrauma, and ventilator-associated pneumonia. After irreversible brain injury and determination of futility of care, the goal of medical management of the donor shifts to maintaining hemodynamic stability and maximizing the likelihood of successful organ recovery.


Assuntos
Transplante de Pulmão , Obtenção de Tecidos e Órgãos , Humanos , Pulmão , Fatores de Tempo , Doadores de Tecidos
7.
Biomedicines ; 10(3)2022 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-35327328

RESUMO

Sepsis and septic shock represent important burdens of disease around the world. Sepsis-associated neurological consequences have a great impact on patients, both in the acute phase and in the long term. Sepsis-associated encephalopathy (SAE) is a severe brain dysfunction that may contribute to long-term cognitive impairment. Its pathophysiology recognizes the following two main mechanisms: neuroinflammation and hemodynamic impairment. Clinical manifestations include different forms of altered mental status, from agitation and restlessness to delirium and deep coma. A definite diagnosis is difficult because of the absence of specific radiological and biological criteria; clinical management is restricted to the treatment of sepsis, focusing on early detection of the infection source, maintenance of hemodynamic homeostasis, and avoidance of metabolic disturbances or neurotoxic drugs.

8.
Biomedicines ; 9(9)2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34572414

RESUMO

The synergic combination of D-dimer (as proxy of thrombotic/vascular injury) and static compliance (as proxy of parenchymal injury) in predicting mortality in COVID-19-ARDS has not been systematically evaluated. The objective is to determine whether the combination of elevated D-dimer and low static compliance can predict mortality in patients with COVID-19-ARDS. A "training sample" (March-June 2020) and a "testing sample" (September 2020-January 2021) of adult patients invasively ventilated for COVID-19-ARDS were collected in nine hospitals. D-dimer and compliance in the first 24 h were recorded. Study outcome was all-cause mortality at 28-days. Cut-offs for D-dimer and compliance were identified by receiver operating characteristic curve analysis. Mutually exclusive groups were selected using classification tree analysis with chi-square automatic interaction detection. Time to death in the resulting groups was estimated with Cox regression adjusted for SOFA, sex, age, PaO2/FiO2 ratio, and sample (training/testing). "Training" and "testing" samples amounted to 347 and 296 patients, respectively. Three groups were identified: D-dimer ≤ 1880 ng/mL (LD); D-dimer > 1880 ng/mL and compliance > 41 mL/cmH2O (LD-HC); D-dimer > 1880 ng/mL and compliance ≤ 41 mL/cmH2O (HD-LC). 28-days mortality progressively increased in the three groups (from 24% to 35% and 57% (training) and from 27% to 39% and 60% (testing), respectively; p < 0.01). Adjusted mortality was significantly higher in HD-LC group compared with LD (HR = 0.479, p < 0.001) and HD-HC (HR = 0.542, p < 0.01); no difference was found between LD and HD-HC. In conclusion, combination of high D-dimer and low static compliance identifies a clinical phenotype with high mortality in COVID-19-ARDS.

9.
Intensive Care Med ; 46(12): 2397-2410, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33175276

RESUMO

PURPOSE: To provide clinical practice recommendations and generate a research agenda on mechanical ventilation and respiratory support in patients with acute brain injury (ABI). METHODS: An international consensus panel was convened including 29 clinician-scientists in intensive care medicine with expertise in acute respiratory failure, neurointensive care, or both, and two non-voting methodologists. The panel was divided into seven subgroups, each addressing a predefined clinical practice domain relevant to patients admitted to the intensive care unit (ICU) with ABI, defined as acute traumatic brain or cerebrovascular injury. The panel conducted systematic searches and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) method was used to evaluate evidence and formulate questions. A modified Delphi process was implemented with four rounds of voting in which panellists were asked to respond to questions (rounds 1-3) and then recommendation statements (final round). Strong recommendation, weak recommendation, or no recommendation were defined when > 85%, 75-85%, and < 75% of panellists, respectively, agreed with a statement. RESULTS: The GRADE rating was low, very low, or absent across domains. The consensus produced 36 statements (19 strong recommendations, 6 weak recommendations, 11 no recommendation) regarding airway management, non-invasive respiratory support, strategies for mechanical ventilation, rescue interventions for respiratory failure, ventilator liberation, and tracheostomy in brain-injured patients. Several knowledge gaps were identified to inform future research efforts. CONCLUSIONS: This consensus provides guidance for the care of patients admitted to the ICU with ABI. Evidence was generally insufficient or lacking, and research is needed to demonstrate the feasibility, safety, and efficacy of different management approaches.


Assuntos
Lesões Encefálicas , Respiração Artificial , Lesões Encefálicas/terapia , Consenso , Cuidados Críticos , Humanos , Unidades de Terapia Intensiva
10.
Minerva Anestesiol ; 86(8): 877-883, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32368883

RESUMO

Intra-abdominal hypertension (IAH) is a common complication in critically ill patients that may lead to multiorgan failure and is associated to worse outcome. Respiratory failure is among the most important consequences of IAH and it is originated by different mechanisms, such as chest wall elastance increase, functional residual capacity reduction, compression atelectasis and lung edema formation through reduction in lymphatic drainage. Many experimental studies showed that total lung capacity and functional residual capacity can be decreased by 40% during abdominal hypertension, while respiratory system and chest wall pressure-volume curves can be significantly shifted downward and to the right. Moreover, the relationship between intra-abdominal volume and airway pressure has been found to be exponential, meaning that small increases in volume can translate in dramatic increases in pressure. Clinical studies confirmed relevant atelectasis in dependent lung regions during IAH, with significant reductions in functional residual capacity and compromised oxygenation. Moreover, sepsis-related capillary leak and fluid overload may aggravate IAH and respiratory failure, thus establishing a dangerous vicious circle. Respiratory management of patients with IAH is challenging and there is no univocal answer. The measurement of intra-abdominal pressure and esophageal pressure (as a surrogate of pleural pressure) may be useful in assessing the condition and guiding mechanical ventilation. Positive end-expiratory pressure (PEEP) must be carefully selected to counteract IAH-related diaphragm displacement, but too high PEEP levels are associated with hemodynamic failure. Continuous negative extra-abdominal pressure is a promising approach, but its clinical application needs more investigation.


Assuntos
Lesão Pulmonar Aguda , Hipertensão Intra-Abdominal , Insuficiência Respiratória , Humanos , Hipertensão Intra-Abdominal/etiologia , Hipertensão Intra-Abdominal/terapia , Respiração com Pressão Positiva , Respiração Artificial
11.
Minerva Anestesiol ; 86(8): 844-852, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32449334

RESUMO

BACKGROUND: Ventilator-associated pneumonia (VAP) is a significant cause of morbidity and mortality in critically ill patients who require mechanical ventilation (MV). Subglottic secretions above the endotracheal cuff are associated with bacteria colonization of lower respiratory tract, causing VAP. A preventive strategy to avoid subglottic secretion progression is the drainage with special tracheal tubes effective in preventing both early onset and late onset VAP. The purpose of this study was to measure VAP incidence in tracheostomized patients with suction above the cuff. METHODS: The authors performed a matched cohort study with historical control in three academic Intensive Care Units (ICUs): upon ICU admission, patients requiring MV were submitted to tracheostomy with a tracheal tube allowing drainage of subglottic secretions (treatment group). A control group without suctioning above the cuff was selected applying the propensity score matching on dataset of previous ELT Study. VAP occurrence at 28-days from intubation was the primary endpoint; hospital mortality and ICU-free days at 28-days were the secondary endpoints. RESULTS: Between July 2014 and April 2016, 125 tracheostomized patients were included in the analysis. 232 tracheostomized patients without suctioning were selected as a control group for the matched cohort study. The application of propensity score matching selected 60 patients to compare the two groups. Incidence of VAP was 8% in treatment group and 19.4% in the control group (P value =0.004). After balance with propensity score matching VAP was 8.3% and 21.7% (P value =0.0408), respectively. CONCLUSIONS: Subglottic secretion drainage reduces incidence of VAP in critically ill patients requiring ongoing MV via tracheostomy.


Assuntos
Pneumonia Associada à Ventilação Mecânica , Estudos de Coortes , Drenagem , Glote , Humanos , Unidades de Terapia Intensiva , Intubação Intratraqueal/efeitos adversos , Pneumonia Associada à Ventilação Mecânica/epidemiologia , Pneumonia Associada à Ventilação Mecânica/prevenção & controle , Respiração Artificial , Traqueostomia
12.
Minerva Anestesiol ; 86(6): 617-626, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31994367

RESUMO

BACKGROUND: Normothermic ex-vivo lung perfusion (EVLP) limits organ donor shortage by potentially using high-risk donor lungs. Microbial burden reduction has been demonstrated after EVLP using antibiotic prophylaxis with imipenem. However, no data have been published on the clinical consequences of the potential residual bacterial burden. METHODS: Imipenem concentration was measured every hour (T0 to T6) in the lung perfusate and at the end of EVLP (Tf) in biopsies. The antimicrobial activity of perfusate at T1 and Tf against E. coli and K. pneumoniae was evaluated. Lungs were distinguished: no bacterial species in recipients and donors (donor-/recipient-); bacterial species isolated from donors and not from recipients (donor+/recipient-); same bacterial species in both recipients and donors (donor+/recipient+). Interleukin 6 (IL-6) and IL-8 concentrations in lung perfusate, clinical pulmonary infection score (CPIS) and primary graft dysfunction (PGD) were evaluated. RESULTS: Imipenem concentration in perfusate decreased over time. T1 and Tf perfusates exhibited bactericidal activity against E. coli and K. pneumoniae. Overall, T1 perfusates yielded higher bactericidal titers (BTs) than Tf. The donor+/recipient+ group (26% of cases) had higher IL-6 and IL-8 in perfusate and higher CPIS. CONCLUSIONS: Recipients with the same bacterial species isolated in their donors had higher risk of pulmonary inflammation and early post-transplant pneumonia. Improvements in antimicrobial strategies during EVLP are warranted to minimize the consequences of donor associated respiratory infection.


Assuntos
Imipenem , Transplante de Pulmão , Biópsia , Escherichia coli , Humanos , Imipenem/farmacologia , Pulmão , Preservação de Órgãos , Perfusão , Doadores de Tecidos
13.
J Crit Care ; 54: 22-29, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31326617

RESUMO

PURPOSE: Critical illness is a life threatening condition inducing a severe acute physical stress. The aim of the study was to investigate the activation of pituitary axis early after ICU admission in patients with critical illnesses of different etiology and its association with outcome. MATERIALS AND METHODS: Patients admitted for acute respiratory distress syndrome (ARDS), severe traumatic brain injury (TBI), subarachnoid hemorrhage (SAH) and neurocritically ill patients at the moment of brain death (BD) diagnosis were included in the present post-hoc analysis. On day 1, 2-3 and 4-5 after admission the following pituitary axes were assessed: hypothalamic-pituitary-adrenal, hypothalamic-pituitary-thyroid, somatotroph, prolactin and copeptin. ICU mortality was used as outcome measure. RESULTS: One hundred-thirteen critical ill patients were studied. Thyroid axis suppression and activation of copeptin axis were the most frequent pituitary hormone alterations, present in almost 60% of patients. Activation of the hypothalamic pituitary adrenal axis was a predictor of ICU mortality independently from the underlying critical illness [OR 3.952 (C.I.95% 1.129-13.838)]. CONCLUSIONS: Pituitary axis function is frequently altered early after ICU admission, the magnitude of hormonal response being different according to the underlying critical illness. The activation of the hypothalamic pituitary adrenal axis was a strong predictor of ICU mortality.


Assuntos
Estado Terminal , Sistema Hipotálamo-Hipofisário , Hipófise/fisiologia , Sistema Hipófise-Suprarrenal , APACHE , Adulto , Idoso , Morte Encefálica , Lesões Encefálicas Traumáticas/complicações , Feminino , Glicopeptídeos/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Admissão do Paciente , Prolactina , Hemorragia Subaracnóidea/complicações , Resultado do Tratamento
14.
Sci Rep ; 9(1): 6090, 2019 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-30988316

RESUMO

Acute kidney injury following traumatic brain injury is associated with poor outcome. We investigated in vitro the effects of plasma of brain injured patients with acute tubular kidney injury on kidney tubular epithelial cell function. we performed a prospective observational clinical study in ICU in a trauma centre of the University hospital in Italy including twenty-three ICU patients with traumatic brain injury consecutively enrolled. Demographic data were recorded on admission: age 39 ± 19, Glasgow Coma Score 5 (3-8). Neutrophil Gelatinase-Associated Lipocalin and inflammatory mediators were measured in plasma on admission and after 24, 48 and 72 hours; urine were collected for immunoelectrophoresis having healthy volunteers as controls. Human renal proximal tubular epithelial cells were stimulated with patients or controls plasma. Adhesion of freshly isolated human neutrophils and trans-epithelial electrical resistance were assessed; cell viability (XTT assay), apoptosis (TUNEL staining), Neutrophil Gelatinase-Associated Lipocalin and Megalin expression (quantitative real-time PCR) were measured. All patients with normal serum creatinine showed increased plasmatic Neutrophil Gelatinase-Associated Lipocalin and increased urinary Retinol Binding Protein and α1-microglobulin. Neutrophil Gelatinase-Associated Lipocalin was significantly correlated with both inflammatory mediators and markers of tubular damage. Patient' plasma incubated with tubular cells significantly increased adhesion of neutrophils, reduced trans-epithelial electrical resistance, exerted a cytotoxic effect and triggered apoptosis and down-regulated the endocytic receptor Megalin compared to control. Plasma of brain injured patients with increased markers of subclinical acute kidney induced a pro-inflammatory phenotype, cellular dysfunction and apoptotic death in tubular epithelial cells.


Assuntos
Injúria Renal Aguda/etiologia , Lesões Encefálicas Traumáticas/complicações , Células Epiteliais/patologia , Túbulos Renais Proximais/citologia , Adulto , Apoptose , Biomarcadores/sangue , Células Cultivadas , Citocinas/sangue , Feminino , Humanos , Túbulos Renais Proximais/patologia , Lipocalina-2/sangue , Proteína-2 Relacionada a Receptor de Lipoproteína de Baixa Densidade/sangue , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
15.
J Heart Lung Transplant ; 38(3): 267-276, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30642797

RESUMO

BACKGROUND: Lung metabolism during ex vivo lung perfusion (EVLP) is increasingly studied. Microdialysis (MD) allows metabolic monitoring by sampling parenchymal interstitial fluid. This study investigated lung metabolism using MD during EVLP and evaluated whether microdialysate metabolites could improve selection and discriminate outcome of donor lungs. METHODS: MD monitoring was used during 14 clinical EVLP procedures. Paired microdialysate and perfusate samples were analyzed for glucose, lactate, pyruvate, glutamate, and the lactate/pyruvate (L/P) ratio, and values that best discriminated an unfavorable outcome were determined. Outcome was defined as unfavorable (lungs not transplanted or transplanted with primary graft dysfunction at 72 hours ≥ 2) or favorable (lungs transplanted with primary graft dysfunction < 2). RESULTS: Microdialysate markers and the perfusate L/P ratio could discriminate unfavorable outcome with sensitivity and specificity of 0.85 and 0.81 for MD glutamate > 18.4 µmol/liter, 0.81 and 0.74 for MD lactate > 685 µmol/liter, 0.92 and 0.75 for MD glucose > 530 µmol/liter, 0.85 and 0.65 for MD pyruvate > 25 µmol/liter, and 0.73 and 0.67 for perfusate L/P ratio > 24.17. All microdialysate markers, perfusate and microdialysate L/P ratio, and perfusate lactate discriminated outcome when we limited analysis only to transplanted lungs. CONCLUSIONS: We report the use of MD to evaluate lung metabolism during clinical EVLP, demonstrating that MD metabolites can contribute to selection of reconditioned lungs and discriminate early outcome after transplantation. Furthermore, glutamate as a marker of lung injury during EVLP is proposed and could hence be used as a potential target for future therapies.


Assuntos
Transplante de Pulmão , Pulmão/metabolismo , Adulto , Estudos de Viabilidade , Glucose/metabolismo , Ácido Glutâmico/metabolismo , Humanos , Técnicas In Vitro , Ácido Láctico/metabolismo , Microdiálise , Pessoa de Meia-Idade , Perfusão , Valor Preditivo dos Testes , Ácido Pirúvico/metabolismo , Resultado do Tratamento , Adulto Jovem
16.
Minerva Anestesiol ; 85(5): 494-504, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30394062

RESUMO

BACKGROUND: During orthotopic liver transplantation (OLT), liver graft ischemia-reperfusion injury (IRI) triggers a cytokine-mediated systemic inflammatory response, which impairs graft function and disrupts distal organ homeostasis. The objective of this prospective, observational trial was to assess the effects of IRI on lung and chest wall mechanics in the intraoperative period of patients undergoing OLT. METHODS: In 26 patients undergoing OLT, we measured elastance of the respiratory system (ERS), partitioned into lung (EL) and chest wall (ECW), hemodynamics, and fluid and blood product intake before laparotomy (T1), after portal/caval surgical clamp (T2), and immediately (T3) and, at 90 and 180 minutes post-reperfusion (T4 and T5, respectively). Interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), IL-1ß and tumor necrosis factor-α plasma concentrations were assessed at T1, T4 and T5. RESULTS: EL significantly decreased from T1 to T2 (13.5±4.4 vs 9.7±4.8 cmH2O/L, P<0.05), remained stable at T3, while at T4 (12.3±4.4 cmH2O/L, P<0.05) was well above levels recorded at T2, reaching its highest value at T5 (15±3.9 cmH2O/L, P<0.05). Variations in ERS, EL, driving pressure (∆P) and trans-pulmonary pressure (∆PL) significantly correlated with changes in IL-6 and MCP-1 plasma concentrations, but not with changes in wedge pressure, fluid amounts, and red blood cells and platelets administered. No correlation was found between changes in cytokine concentrations and ECW. CONCLUSIONS: We found that EL, ECW, ∆P and ∆PL underwent significant variations during the OLT procedure. Further, we documented a significant association between the respiratory mechanics changes and the inflammatory response following liver graft reperfusion.


Assuntos
Circulação Hepática , Transplante de Fígado , Traumatismo por Reperfusão/fisiopatologia , Mecânica Respiratória , Citocinas/sangue , Feminino , Hemodinâmica , Humanos , Complicações Intraoperatórias/fisiopatologia , Laparotomia , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Pressão Propulsora Pulmonar , Síndrome de Resposta Inflamatória Sistêmica/fisiopatologia , Parede Torácica/fisiopatologia
17.
Minerva Anestesiol ; 84(2): 204-215, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28895380

RESUMO

Over the last two decades, lung transplantation emerged as the standard of care for patients with advanced and terminal lung disease. Despite the increment in lung transplantation rates, in 2016 the overall mortality while on waiting list in Italy reached 10%, whereas only 39% of the wait-list patients were successfully transplanted. A number of approaches, including protective ventilatory strategy, accurate management of fluid balance, and administration of a hormonal resuscitation therapy, have been reported to improve lung donor performance before organ retrieval. These approaches, in conjunction with the use of ex-vivo lung perfusion technique contributed to expand the lung donor pool, without affecting the harvest of other organs and the outcomes of lung recipients. However, the efficacy of issues related to the ex-vivo lung perfusion technique, such as the optimal ventilation strategy, the ischemia-reperfusion induced lung injury management, the prophylaxis of germs transmission from donor to recipient and the application of targeted pharmacologic therapies to treat specific donor lung injuries are still to be explored. The main objective of the present review is to summarize the "state-of-art" strategies to optimize the donor lungs and to present the actual role of ex-vivo lung perfusion in the process of lung transplant. Moreover, different approaches about the technique reported in literature and several issues that are under investigation to treat specific donor lung injury will be discussed.


Assuntos
Transplante de Pulmão , Preservação de Órgãos/normas , Obtenção de Tecidos e Órgãos/normas , Humanos
18.
Curr Opin Crit Care ; 24(1): 29-34, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29135616

RESUMO

PURPOSE OF REVIEW: Aim of this article is to review evidence recently generated on the application of extracorporeal carbon dioxide removal (ECCO2R) in patients with acute exacerbation of chronic obstructive pulmonary disease (COPD) requiring mechanical ventilation (invasive and non invasive) for hypercapnic respiratory failure. RECENT FINDINGS: To date, the paucity of evidences on ECCO2R to decrease the rate of noninvasive ventilation (NIV) failure and to wean hypercapnic patients from invasive mechanical ventilation (IMV) precludes to systematically apply this technology to COPD patients. SUMMARY: Although several efforts have been made to reduce invasiveness and to improve the efficiency of extracorporeal systems, further randomized studies are needed to assess the effects of this technique on both short-term and long-term clinical outcomes.


Assuntos
Dióxido de Carbono/sangue , Circulação Extracorpórea/métodos , Oxigenação por Membrana Extracorpórea , Hipercapnia/terapia , Ventilação não Invasiva , Doença Pulmonar Obstrutiva Crônica/terapia , Medicina Baseada em Evidências , Oxigenação por Membrana Extracorpórea/métodos , Humanos , Hipercapnia/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Mecânica Respiratória/fisiologia
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