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The gut microbiome has an important role in infant health and development. We characterized the fecal microbiome and metabolome of 222 young children in Dhaka, Bangladesh during the first two years of life. A distinct Bifidobacterium longum clade expanded with introduction of solid foods and harbored enzymes for utilizing both breast milk and solid food substrates. The clade was highly prevalent in Bangladesh, present globally (at lower prevalence), and correlated with many other gut taxa and metabolites, indicating an important role in gut ecology. We also found that the B. longum clades and associated metabolites were implicated in childhood diarrhea and early growth, including positive associations between growth measures and B. longum subsp. infantis, indolelactate and N-acetylglutamate. Our data demonstrate geographic, cultural, seasonal, and ecological heterogeneity that should be accounted for when identifying microbiome factors implicated in and potentially benefiting infant development.
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Bifidobacterium longum , Lactente , Criança , Feminino , Humanos , Pré-Escolar , Bifidobacterium longum/metabolismo , Bifidobacterium/metabolismo , Desmame , Oligossacarídeos/metabolismo , Bangladesh , Leite Humano , Fezes/microbiologiaRESUMO
The steep rise in food allergy (FA) has evoked environmental factors involved in disease pathogenesis, including the gut microbiota, diet, and their metabolites. Early introduction of solid foods synchronizes with the "weaning reaction," a time during which the microbiota imprints durable oral tolerance. Recent work has shown that children with FA manifest an early onset dysbiosis with the loss of Clostridiales species, which promotes the differentiation of ROR-γt+ regulatory T cells to suppress FA. This process can be reversed in pre-clinical mouse models by targeted bacteriotherapy. Here, we review the dominant tolerance mechanisms enforced by the microbiota to suppress FA and discuss therapeutic intervention strategies that act to recapitulate the early life window of opportunity in stemming the FA epidemic.
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Dieta , Disbiose/microbiologia , Hipersensibilidade Alimentar/imunologia , Microbioma Gastrointestinal/fisiologia , Animais , Clostridiales/isolamento & purificação , Dessensibilização Imunológica/métodos , Humanos , Tolerância Imunológica/imunologia , Imunoglobulina E/imunologia , Camundongos , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Linfócitos T Reguladores/citologia , Linfócitos T Reguladores/imunologiaRESUMO
Microbes colonize all body surfaces at birth and participate in the development of the immune system. In newborn mammals, the intestinal microbiota is first shaped by the dietary and immunological components of milk and then changes upon the introduction of solid food during weaning. Here, we explored the reactivity of the mouse intestinal immune system during the first weeks after birth and into adulthood. At weaning, the intestinal microbiota induced a vigorous immune response-a "weaning reaction"-that was programmed in time. Inhibition of the weaning reaction led to pathological imprinting and increased susceptibility to colitis, allergic inflammation, and cancer later in life. Prevention of this pathological imprinting was associated with the generation of RORγt+ regulatory T cells, which required bacterial and dietary metabolites-short-chain fatty acids and retinoic acid. Thus, the weaning reaction to microbiota is required for immune ontogeny, the perturbation of which leads to increased susceptibility to immunopathologies later in life.
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Microbioma Gastrointestinal/imunologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Linfócitos T Reguladores/imunologia , Desmame , Animais , Animais Recém-Nascidos/imunologia , Animais Recém-Nascidos/microbiologia , Ácidos Graxos Voláteis/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Tretinoína/metabolismoRESUMO
The gut microbiota is well known to possess immunomodulatory capacities, influencing a multitude of cellular signalling pathways to maintain host homeostasis. Although the formation of the immune system initiates before birth in a sterile environment, an emerging body of literature indicates that the neonatal immune system is influenced by a first wave of external stimuli that includes signals from the maternal microbiota. A second wave of stimulus begins after birth and must be tightly regulated during the neonatal period when colonization of the host occurs concomitantly with the maturation of the immune system, requiring a fine adjustment between establishing tolerance towards the commensal microbiota and preserving inflammatory responses against pathogenic invaders. Besides integrating cues from commensal microbes, the neonatal immune system must also regulate responses triggered by other environmental signals, such as dietary antigens, which become more complex with the introduction of solid food during the weaning period. This "window of opportunity" in early life is thought to be crucial for the proper development of the immune system, setting the tone of subsequent immune responses in adulthood and modulating the risk of developing chronic and metabolic inflammatory diseases. Here we review the importance of host-microbiota interactions for the development and maturation of the immune system, particularly in the early-life period, highlighting the known mechanisms involved in such communication. This discussion is focused on recent data demonstrating microbiota-mediated education of innate immune cells and its role in the development of lymphoid tissues.
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Rationale: Airway occlusion pressure at 100 ms (P0.1) reflects central respiratory drive. Objectives: We aimed to assess factors associated with P0.1 and whether an abnormally low or high P0.1 value is associated with higher mortality and longer duration of mechanical ventilation (MV). Methods: We performed a secondary analysis of a prospective cohort study conducted in 10 ICUs in France to evaluate dyspnea in communicative MV patients. In patients intubated for more than 24 hours, P0.1 was measured with dyspnea as soon as patients could communicate and the next day. Measurements and Main Results: Among 260 patients assessed after a median time of ventilation of 4 days, P0.1 was 1.9 (1-3.5) cm H2O at enrollment, 24% had P0.1 values >3.5 cm H2O, 37% had P0.1 values between 1.5 and 3.5 cm H2O, and 39% had P0.1 values <1.5 cm H2O. In multivariable linear regression, independent factors associated with P0.1 were the presence of dyspnea (P = 0.037), respiratory rate (P < 0.001), and PaO2 (P = 0.008). Ninety-day mortality was 33% in patients with P0.1 > 3.5 cm H2O versus 19% in those with P0.1 between 1.5 and 3.5 cm H2O and 17% in those with P0.1 < 1.5 cm H2O (P = 0.046). After adjustment for the main risk factors, P0.1 was associated with 90-day mortality (hazard ratio per 1 cm H2O, 1.19 [95% confidence interval, 1.04-1.37]; P = 0.011). P0.1 was also independently associated with a longer duration of MV (hazard ratio per 1 cm H2O, 1.10 [95% confidence interval, 1.02-1.19]; P = 0.016). Conclusions: In patients receiving invasive MV, abnormally high P0.1 values may suggest dyspnea and are associated with higher mortality and prolonged duration of MV.
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Estado Terminal , Dispneia , Respiração Artificial , Humanos , Masculino , Dispneia/mortalidade , Dispneia/etiologia , Feminino , Estudos Prospectivos , Estado Terminal/mortalidade , Pessoa de Meia-Idade , Idoso , França/epidemiologia , Obstrução das Vias Respiratórias/mortalidade , Obstrução das Vias Respiratórias/terapia , Unidades de Terapia Intensiva/estatística & dados numéricos , Estudos de CoortesRESUMO
BACKGROUND: Randomized controlled trials have demonstrated that early introduction of allergenic foods, such as peanut and egg, can reduce food allergy in high-risk children. Many international guidelines recommend introduction of allergenic foods in the first year of life, and accordingly, the Swedish National Food agency released updated guidelines in June 2019. OBJECTIVE: Our aim was to examine whether the age at introduction and consumption frequency of allergenic foods have changed since release of the revised national guidelines on the introduction of solid foods in Sweden. METHODS: Children born between June 2016 and December 2018 (n = 1925) were compared with children born between June 2019 and April 2021 (n = 1761) by using data from the NorthPop Birth Cohort study. Data on food introduction, eczema, and food allergy were prospectively collected until age 18 months by using web-based questionnaires. IgE sensitization was assessed at 18 age months. RESULTS: The proportion of participants who had been introduced to egg, legume, soy products, peanut, almond, and cashew nut during the first year of life increased after implementation of the revised national guidelines. The most significant changes were seen for legume (from 55.2% to 69.8% [adjusted odds ratio = 1.90 (95% CI = 1.62-2.24)]) and peanut (from 29.2% to 43.2% adjusted odds ratio = 1.87 (95% CI = 1.55-2.24)]); consumption frequency had also increased. No differences in the prevalence of eczema, food allergy, or sensitization to the foods of interest were found. CONCLUSION: Since release of the revised guidelines, infants in the general population are introduced to and consume a variety of allergenic foods earlier and more frequently; however, early manifestations of allergic disease have remained unchanged.
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Eczema , Hipersensibilidade Alimentar , Lactente , Criança , Humanos , Suécia/epidemiologia , Estudos de Coortes , Hipersensibilidade Alimentar/epidemiologia , Hipersensibilidade Alimentar/complicações , Alimentos , Eczema/epidemiologia , Eczema/complicações , Arachis , AlérgenosRESUMO
We describe cases of intestinal failure wherein inpatient admission was critical toward enteral autonomy. We performed a retrospective chart review of 6 children with long-term parenteral nutrition dependence who were weaned from parenteral nutrition following admission. Admissions included feeding and medication titration, interdisciplinary care, and home parenteral nutrition team consultation.
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BACKGROUND: Clinical evidence regarding predictors of successful weaning from mechanical circulatory support (MCS) is lacking. This study aimed to create a simple risk score to predict successful weaning from MCS in patients with cardiogenic shock. METHODS: This retrospective single-center cohort study included 114 consecutive patients with cardiogenic shock treated with veno-arterial extracorporeal membrane oxygenation or IMPELLA between January 2013 and June 2023. Patients with out-of-hospital cardiac arrest were excluded. The primary endpoint was successful weaning from MCS defined as successful decannulation without the need for MCS re-implantation and survival to discharge. Multivariable logistic regression with a stepwise variable selection was performed to generate the prediction model. We first developed a general weaning score model, and then created a simple version of the score model using the same variables. RESULTS: Fifty-five patients were successfully weaned from MCS. The following variables measured during weaning evaluation were selected as the components of the weaning score model: acute myocardial infarction (AMI), mean blood pressure, left ventricular ejection fraction (LVEF), lactate level, and QRS duration. According to the results, we conducted a novel weaning score model to predict successful weaning from MCS: 1.774-2.090×(AMI)+0.062×[mean blood pressure (mmHg)]+0.139×[LVEF (%)]-0.322×[Lactate (mg/dl)]-0.066×[QRS (msec)]. The following variables were selected as the components of the simple version of the weaning score model: AMI, mean blood pressure ≥80 mmHg, lactate <10 mg/dL, QRS duration ≤95 msec, and LVEF >35%. CONCLUSIONS: We developed a simple model to predict successful weaning from MCS in patients with cardiogenic shock.
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BACKGROUND: Although multidrug-resistant bacteria (MDR) are common in patients undergoing prolonged weaning, there is little data on their impact on weaning and patient outcomes. METHODS: This is a retrospective analysis of consecutive patients who underwent prolonged weaning and were at a university weaning centre from January 2018 to December 2020. The influence of MDR colonisation and infection on weaning success (category 3a and 3b), successful prolonged weaning from invasive mechanical ventilation (IMV) with or without the need for non-invasive ventilation (NIV) compared with category 3c (weaning failure 3cI or death 3cII) was investigated. The pathogen groups considered were: multidrug-resistant gram-negative bacteria (MDRGN), methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus spp. (VRE). RESULTS: A total of 206 patients were studied, of whom 91 (44.2%) showed evidence of MDR bacteria (32% VRE, 1.5% MRSA and 16% MDRGN), with 25 patients also meeting the criteria for MDR infection. 70.9% of the 206 patients were successfully weaned from IMV, 8.7% died. In 72.2% of cases, nosocomial pneumonia and other infections were the main cause of death. Patients with evidence of MDR (infection and colonisation) had a higher incidence of weaning failure than those without evidence of MDR (48% vs. 34.8% vs. 21.7%). In multivariate analyses, MDR infection (OR 4.9, p = 0.004) was an independent risk factor for weaning failure, along with male sex (OR 2.3, p = 0.025), Charlson Comorbidity Index (OR 1.2, p = 0.027), pH (OR 2.7, p < 0.001) and duration of IMV before admission (OR 1.01, p < 0.001). In addition, MDR infection was the only independent risk factor for death (category 3cII), (OR 6.66, p = 0.007). CONCLUSION: Patients with MDR infection are significantly more likely to die during the weaning process. There is an urgent need to develop non-antibiotic approaches for the prevention and treatment of MDR infections as well as clinical research on antibiotic stewardship in prolonged weaning as well as in ICUs.
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Staphylococcus aureus Resistente à Meticilina , Respiração Artificial , Humanos , Masculino , Respiração Artificial/efeitos adversos , Estudos Retrospectivos , Desmame do Respirador , Bactérias , Antibacterianos/uso terapêuticoRESUMO
BACKGROUND: Long-term invasive mechanical ventilation (IMV) is a major burden for those affected and causes high costs for the health care system. Early risk assessment is a prerequisite for the best possible support of high-risk patients during the weaning process. We aimed to identify risk factors for long-term IMV within 96 h (h) after the onset of IMV. METHODS: The analysis was based on data from one of Germany's largest statutory health insurance funds; patients who received IMV ≥ 96 h and were admitted in January 2015 at the earliest and discharged in December 2017 at the latest were analysed. OPS and ICD codes of IMV patients were considered, including the 365 days before intubation and 30 days after discharge. Long-term IMV was defined as evidence of invasive home mechanical ventilation (HMV), IMV ≥ 500 h, or readmission with (re)prolonged ventilation. RESULTS: In the analysis of 7758 hospitalisations, criteria for long-term IMV were met in 38.3% of cases, of which 13.9% had evidence of HMV, 73.1% received IMV ≥ 500 h and/or 40.3% were re-hospitalised with IMV. Several independent risk factors were identified (p < 0.005 each), including pre-diagnoses such as pneumothorax (OR 2.10), acute pancreatitis (OR 2.64), eating disorders (OR 1.99) or rheumatic mitral valve disease (OR 1.89). Among ICU admissions, previous dependence on an aspirator or respirator (OR 5.13), and previous tracheostomy (OR 2.17) were particularly important, while neurosurgery (OR 2.61), early tracheostomy (OR 3.97) and treatment for severe respiratory failure such as positioning treatment (OR 2.31) and extracorporeal lung support (OR 1.80) were relevant procedures in the first 96 h after intubation. CONCLUSION: This comprehensive analysis of health claims has identified several risk factors for the risk of long-term ventilation. In addition to the known clinical risks, the information obtained may help to identify patients at risk at an early stage. Trial registration The PRiVENT study was retrospectively registered at ClinicalTrials.gov (NCT05260853). Registered at March 2, 2022.
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Ventilação não Invasiva , Pancreatite , Humanos , Respiração Artificial/efeitos adversos , Respiração Artificial/métodos , Estudos Longitudinais , Doença Aguda , Fatores de RiscoRESUMO
BACKGROUND: The endeavor of liberating patients from ventilator dependence within respiratory care centers (RCCs) poses considerable challenges. Multiple factors contribute to this process, yet establishing an effective regimen for pulmonary rehabilitation (PR) remains uncertain. This retrospective study aimed to evaluate existing rehabilitation protocols, ascertain associations between clinical factors and patient outcomes, and explore the influence of these protocols on the outcomes of the patients to shape suitable rehabilitation programs. METHODS: Conducted at a medical center in northern Taiwan, the retrospective study examined 320 newly admitted RCC patients between January 1, 2015, and December 31, 2017. Each patient received a tailored PR protocol, following which researchers evaluated weaning rates, RCC survival, and 3-month survival as outcome variables. Analyses scrutinized differences in baseline characteristics and prognoses among three PR protocols: protocol 1 (routine care), protocol 2 (routine care plus breathing training), and protocol 3 (routine care plus breathing and limb muscle training). RESULTS: Among the patients, 28.75% followed protocol 1, 59.37% protocol 2, and 11.88% protocol 3. Variances in age, body-mass index, pneumonia diagnosis, do-not-resuscitate orders, Glasgow Coma Scale scores (≤ 14), and Acute Physiology and Chronic Health Evaluation II (APACHE) scores were notable across these protocols. Age, APACHE scores, and abnormal blood urea nitrogen levels (> 20 mg/dL) significantly correlated with outcomes-such as weaning, RCC survival, and 3-month survival. Elevated mean hemoglobin levels linked to increased weaning rates (p = 0.0065) and 3-month survival (p = 0.0102). Four adjusted models clarified the impact of rehabilitation protocols. Notably, the PR protocol 3 group exhibited significantly higher 3-month survival rates compared to protocol 1, with odds ratios (ORs) ranging from 3.87 to 3.97 across models. This association persisted when comparing with protocol 2, with ORs between 3.92 and 4.22. CONCLUSION: Our study showed that distinct PR protocols significantly affected the outcomes of ventilator-dependent patients within RCCs. The study underlines the importance of tailored rehabilitation programs and identifies key clinical factors influencing patient outcomes. Recommendations advocate prospective studies with larger cohorts to comprehensively assess PR effects on RCC patients.
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Respiração Artificial , Desmame do Respirador , Humanos , Estudos Retrospectivos , Masculino , Feminino , Desmame do Respirador/métodos , Idoso , Pessoa de Meia-Idade , Resultado do Tratamento , Respiração Artificial/métodos , Taiwan/epidemiologia , Estudos de Coortes , Protocolos Clínicos , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: Prolonged weaning from mechanical ventilation is associated with poor clinical outcome. Therefore, choosing the right moment for weaning and extubation is essential. Electrical Impedance Tomography (EIT) is a promising innovative lung monitoring technique, but its role in supporting weaning decisions is yet uncertain. We aimed to evaluate physiological trends during a T-piece spontaneous breathing trail (SBT) as measured with EIT and the relation between EIT parameters and SBT success or failure. METHODS: This is an observational study in which twenty-four adult patients receiving mechanical ventilation performed an SBT. EIT monitoring was performed around the SBT. Multiple EIT parameters including the end-expiratory lung impedance (EELI), delta Tidal Impedance (ΔZ), Global Inhomogeneity index (GI), Rapid Shallow Breathing Index (RSBIEIT), Respiratory Rate (RREIT) and Minute Ventilation (MVEIT) were computed on a breath-by-breath basis from stable tidal breathing periods. RESULTS: EELI values dropped after the start of the SBT (p < 0.001) and did not recover to baseline after restarting mechanical ventilation. The ΔZ dropped (p < 0.001) but restored to baseline within seconds after restarting mechanical ventilation. Five patients failed the SBT, the GI (p = 0.01) and transcutaneous CO2 (p < 0.001) values significantly increased during the SBT in patients who failed the SBT compared to patients with a successful SBT. CONCLUSION: EIT has the potential to assess changes in ventilation distribution and quantify the inhomogeneity of the lungs during the SBT. High lung inhomogeneity was found during SBT failure. Insight into physiological trends for the individual patient can be obtained with EIT during weaning from mechanical ventilation, but its role in predicting weaning failure requires further study.
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Impedância Elétrica , Tomografia , Desmame do Respirador , Humanos , Desmame do Respirador/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Tomografia/métodos , Monitorização Fisiológica/métodos , Adulto , Respiração Artificial/métodos , Respiração , Idoso de 80 Anos ou mais , Pulmão/fisiopatologia , Pulmão/diagnóstico por imagem , Pulmão/fisiologiaRESUMO
INTRODUCTION: Tracheostomy decannulation is a routine procedure in airway management. There is no standard decannulation method; however, the two commonly practiced approaches are tracheostomy downsizing and intermittent capping, which are both accompanied by multiple visits to the clinic and increase patient discomfort. Herein, we explore fiberoptic bronchoscopy application in a novel single-stage decannulation protocol. METHODS: We conducted a retrospective study on tracheostomy patients eligible for decannulation. Fiberoptic bronchoscopy was performed on patients with spontaneous ventilation for ≥48 h, age ≥18, hemodynamic stability, normal chest X-ray, adequate swallowing, effective cough, adequate consciousness, patent speaking valve, and absent history of recurrent aspiration. Tracheostomy removal occurred after evaluating the airway and ruling out tracheomalacia, tracheitis with stenosis, obstructive granulation tissue, and moderate-to-severe stenosis. We documented patients' demographic and clinical information, along with details of their post-decannulation course. RESULTS: Out of 58 patients admitted for tracheostomy removal, we excluded six patients (10.3%) from the study because, despite clinical indications for successful weaning, they exhibited abnormalities that interrupted the decannulation process. Of the remaining 52 patients, 50 (96.1%) were successfully weaned off, while two needed reinsertion during their hospital course. Bronchoscopy findings were unremarkable in 33 (63.5%) patients, and the most frequently observed abnormalities were paucity of vocal cord movement in 5 (9.6%) patients and granulation tissue formation in 5 (9.6%) patients. No further airway management was necessary after discharge. CONCLUSIONS: Our study introduces the innovative approach of single-stage bronchoscopic decannulation as a potentially beneficial tool for immediate decannulation. Based on our experience, we achieved a relatively satisfactory outcome following single-stage tracheostomy decannulation with bronchoscopy. The approach shows promise in providing valuable airway insights and predicting possible decannulation failures. Further research is needed to evaluate its impact on stress reduction for patients and surgeons, its superiority compared to traditional techniques, its long-term effects on healthcare, and its potential cost-effectiveness.
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The effect of changes in immunosuppressive therapy during the acute phase post-heart transplantation (HTx) on clinical outcomes remains unclear. This study aimed to investigate the effects of changes in immunosuppressive therapy by corticosteroid (CS) weaning and everolimus (EVR) initiation during the first year post-HTx on clinical outcomes. We analyzed 622 recipients registered in the Korean Organ Transplant Registry (KOTRY) between January 2014 and December 2021. The median age at HTx was 56 years (interquartile range [IQR], 45-62), and the median follow-up time was 3.9 years (IQR 2.0-5.1). The early EVR initiation within the first year post-HTx and maintenance during the follow-up is associated with reduced the risk of primary composite outcome (all-cause mortality or re-transplantation) (HR, 0.24; 95% CI 0.09-0.68; p < 0.001) and cardiac allograft vasculopathy (CAV) (HR, 0.39; 95% CI 0.19-0.79; p = 0.009) compared with EVR-free or EVR intermittent treatment regimen, regardless of CS weaning. However, the early EVR initiation tends to increase the risk of acute allograft rejection compared with EVR-free or EVR intermittent treatment.
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Corticosteroides , Everolimo , Rejeição de Enxerto , Transplante de Coração , Imunossupressores , Sistema de Registros , Humanos , Everolimo/administração & dosagem , Everolimo/uso terapêutico , Transplante de Coração/efeitos adversos , Pessoa de Meia-Idade , Masculino , Feminino , Imunossupressores/uso terapêutico , Imunossupressores/administração & dosagem , República da Coreia/epidemiologia , Rejeição de Enxerto/prevenção & controle , Corticosteroides/administração & dosagem , Corticosteroides/uso terapêutico , Resultado do Tratamento , Sobrevivência de Enxerto , Estudos RetrospectivosRESUMO
BACKGROUND: Midodrine has been used in the intensive care unit (ICU) setting to reduce the time to vasopressor discontinuation. The limited data supporting midodrine use have led to variability in the pattern of initiation and discontinuation of midodrine. OBJECTIVES: To compare the effectiveness and safety of 2 midodrine discontinuation regimens during weaning vasopressors in critically ill patients. METHODS: A retrospective cohort study was conducted at King Abdulaziz Medical City. Included patients were adults admitted to ICU who received midodrine after being unable to be weaned from intravenous vasopressors for more than 24 hours. Patients were categorized into two subgroups depending on the pattern of midodrine discontinuation (tapered dosing regimen vs. nontapered regimen). The primary endpoint was the incidence of inotropes and vasopressors re-initiation after midodrine discontinuation. RESULTS: The incidence of inotropes or vasopressors' re-initiation after discontinuation of midodrine was lower in the tapering group (15.4%) compared with the non-tapering group (40.7%) in the crude analysis as well as regression analysis (odd ratio [OR] = 0.15; 95% CI = 0.03, 0.73, P = 0.02). The time required for the antihypertensive medication(s) initiation after midodrine discontinuation was longer in patients who had dose tapering (beta coefficient (95% CI): 3.11 (0.95, 5.28), P = 0.005). Moreover, inotrope or vasopressor requirement was lower 24 hours post midodrine initiation. In contrast, the two groups had no statistically significant differences in 30-day mortality, in-hospital mortality, or ICU length of stay. CONCLUSION AND RELEVANCE: These real-life data showed that tapering midodrine dosage before discontinuation in critically ill patients during weaning from vasopressor aids in reducing the frequency of inotrope or vasopressor re-initiation. Application of such a strategy might be a reasonable approach among ICU patients unless contraindicated.
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Midodrina , Adulto , Humanos , Midodrina/efeitos adversos , Estudos Retrospectivos , Estado Terminal/terapia , Vasoconstritores , Hospitalização , Unidades de Terapia IntensivaRESUMO
BACKGROUND: In mechanically ventilated patients, diaphragm ultrasound can identify diaphragm weakness and predict weaning failure. We evaluated whether a novel operator-independent ultrasound-based medical device allowing continuous monitoring of the diaphragm (CUSdi) could reliably (1) measure diaphragm excursion (EXdi) and peak contraction velocity (PCVdi), (2) predict weaning outcome, and (3) approximate transdiaphragmatic pressure (Pdi). METHODS: In 49 mechanically ventilated patients, CUSdi was recorded during a 30-min spontaneous breathing trial (SBT), and EXdi and PCVdi were measured. In subgroups of patients, standard ultrasound measurement of EXdi and PCVdi was performed (n = 36), and Pdi derived parameters (peak and pressure time product, n = 30) were measured simultaneously. RESULTS: The agreement bias between standard ultrasound and CUSdi for EXdi was 0.1 cm (95% confidence interval -0.7-0.9 cm). The regression of Passing-Bablok indicated a lack of systematic difference between EXdi measured with standard ultrasound and CUSdi, which were positively correlated (Rho = 0.84, p < 0.001). Weaning failure was observed in 54% of patients. One, two and three minutes after the onset of the SBT, EXdi was higher in the weaning success group than in the failure group. Two minutes after the onset of the SBT, an EXdi < 1.1 cm predicted weaning failure with a sensitivity of 0.83, a specificity of 0.68, a positive predictive value of 0.76, and a negative predictive value of 0.24. There was a weak correlation between EXdi and both peak Pdi (r = 0.22, 95% confidence interval 0.15 - 0.28) and pressure time product (r = 0.13, 95% confidence interval 0.06 - 0.20). Similar results were observed with PCVdi. CONCLUSIONS: Operator-independent continuous diaphragm monitoring quantifies EXdi reliably and can predict weaning failure with an identified cut-off value of 1.1 cm. Trial registration clinicaltrial.gov, NCT04008875 (submitted 12 April 2019, posted 5 July 2019) and NCT03896048 (submitted 27 March 2019, posted 29 March 2019).
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Diafragma , Ultrassonografia , Desmame do Respirador , Humanos , Desmame do Respirador/métodos , Desmame do Respirador/normas , Diafragma/diagnóstico por imagem , Diafragma/fisiopatologia , Estudos Prospectivos , Masculino , Feminino , Ultrassonografia/métodos , Ultrassonografia/normas , Pessoa de Meia-Idade , Idoso , Monitorização Fisiológica/métodos , Monitorização Fisiológica/instrumentação , Respiração Artificial/métodos , Valor Preditivo dos TestesRESUMO
BACKGROUND: The spontaneous breathing trial (SBT) technique that best balance successful extubation with the risk for reintubation is unknown. We sought to determine the comparative efficacy and safety of alternative SBT techniques. METHODS: We searched Medline, EMBASE, and the Cochrane Central Register of Controlled Trials from inception to February 2023 for randomized or quasi-randomized trials comparing SBT techniques in critically ill adults and children and reported initial SBT success, successful extubation, reintubation (primary outcomes) and mortality (ICU, hospital, most protracted; secondary outcome) rates. Two reviewers screened, reviewed full-texts, and abstracted data. We performed frequentist random-effects network meta-analysis. RESULTS: We included 40 RCTs (6716 patients). Pressure Support (PS) versus T-piece SBTs was the most common comparison. Initial successful SBT rates were increased with PS [risk ratio (RR) 1.08, 95% confidence interval (CI) (1.05-1.11)], PS/automatic tube compensation (ATC) [1.12 (1.01 -1.25), high flow nasal cannulae (HFNC) [1.07 (1.00-1.13) (all moderate certainty), and ATC [RR 1.11, (1.03-1.20); low certainty] SBTs compared to T-piece SBTs. Similarly, initial successful SBT rates were increased with PS, ATC, and PS/ATC SBTs compared to continuous positive airway pressure (CPAP) SBTs. Successful extubation rates were increased with PS [RR 1.06, (1.03-1.09); high certainty], ATC [RR 1.13, (1.05-1.21); moderate certainty], and HFNC [RR 1.06, (1.02-1.11); high certainty] SBTs, compared to T-piece SBTs. There was little to no difference in reintubation rates with PS (vs. T-piece) SBTs [RR 1.05, (0.91-1.21); low certainty], but increased reintubation rates with PS [RR 2.84, (1.61-5.03); moderate certainty] and ATC [RR 2.95 (1.57-5.56); moderate certainty] SBTs compared to HFNC SBTs. CONCLUSIONS: SBTs conducted with pressure augmentation (PS, ATC, PS/ATC) versus without (T-piece, CPAP) increased initial successful SBT and successful extubation rates. Although SBTs conducted with PS or ATC versus HFNC increased reintubation rates, this was not the case for PS versus T-piece SBTs.
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Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Extubação/métodos , Extubação/estatística & dados numéricos , Desmame do Respirador/métodos , Desmame do Respirador/estatística & dados numéricos , Desmame do Respirador/normasRESUMO
BACKGROUND: Several bedside assessments are used to evaluate respiratory muscle function and to predict weaning from mechanical ventilation in patients on the intensive care unit. It remains unclear which assessments perform best in predicting weaning success. The primary aim of this systematic review and meta-analysis was to summarize and compare the accuracy of the following assessments to predict weaning success: maximal inspiratory (PImax) and expiratory pressures, diaphragm thickening fraction and excursion (DTF and DE), end-expiratory (Tdiee) and end-inspiratory (Tdiei) diaphragm thickness, airway occlusion pressure (P0.1), electrical activity of respiratory muscles, and volitional and non-volitional assessments of transdiaphragmatic and airway opening pressures. METHODS: Medline (via Pubmed), EMBASE, Web of Science, Cochrane Library and CINAHL were comprehensively searched from inception to 04/05/2023. Studies including adult mechanically ventilated patients reporting data on predictive accuracy were included. Hierarchical summary receiver operating characteristic (HSROC) models were used to estimate the SROC curves of each assessment method. Meta-regression was used to compare SROC curves. Sensitivity analyses were conducted by excluding studies with high risk of bias, as assessed with QUADAS-2. Direct comparisons were performed using studies comparing each pair of assessments within the same sample of patients. RESULTS: Ninety-four studies were identified of which 88 studies (n = 6296) reporting on either PImax, DTF, DE, Tdiee, Tdiei and P0.1 were included in the meta-analyses. The sensitivity to predict weaning success was 63% (95% CI 47-77%) for PImax, 75% (95% CI 67-82%) for DE, 77% (95% CI 61-87%) for DTF, 74% (95% CI 40-93%) for P0.1, 69% (95% CI 13-97%) for Tdiei, 37% (95% CI 13-70%) for Tdiee, at fixed 80% specificity. Accuracy of DE and DTF to predict weaning success was significantly higher when compared to PImax (p = 0.04 and p < 0.01, respectively). Sensitivity and direct comparisons analyses showed that the accuracy of DTF to predict weaning success was significantly higher when compared to DE (p < 0.01). CONCLUSIONS: DTF and DE are superior to PImax and DTF seems to have the highest accuracy among all included respiratory muscle assessments for predicting weaning success. Further studies aiming at identifying the optimal threshold of DTF to predict weaning success are warranted. TRIAL REGISTRATION: PROSPERO CRD42020209295, October 15, 2020.
Assuntos
Respiração Artificial , Desmame do Respirador , Adulto , Humanos , Desmame do Respirador/métodos , Músculos Respiratórios , Diafragma , Curva ROCRESUMO
We evaluated patients aged 12-20 on dupilumab 300 mg weekly for treatment of eosinophilic esophagitis (EoE) who had ≥1 follow-up endoscopy at a tertiary care pediatric hospital (n = 18). Fifty percent had inflammatory EoE (n = 9), 22% had fibrostenotic EoE (n = 4), and 28% had non-EoE eosinophilic gastrointestinal disease (EGID) with esophageal involvement (n = 5). Ninety-four percent discontinued topical corticosteroids (TCS) 2-4 weeks after starting dupilumab. Eighty-nine percent of inflammatory EoE patients had histological response (<15 eosinophils/high-powered field) after an average of 19.1 weeks. One hundred percent of patients with fibrostenotic disease exhibited histological response after 16.8 weeks. Of patients with non-EoE EGID, 60% achieved esophageal histological response after an average of 40.1 weeks. In a small cohort, dupilumab was very effective for adolescent inflammatory and fibrostenotic EoE despite rapid weaning of TCS. Dupilumab was also somewhat effective for non-EoE EGID with esophageal involvement; however, a longer duration of therapy was required.
Assuntos
Anticorpos Monoclonais Humanizados , Esofagite Eosinofílica , Humanos , Esofagite Eosinofílica/tratamento farmacológico , Anticorpos Monoclonais Humanizados/uso terapêutico , Adolescente , Masculino , Feminino , Criança , Adulto Jovem , Resultado do Tratamento , Eosinofilia/tratamento farmacológico , Gastrite/tratamento farmacológico , Esôfago/patologia , Enterite/tratamento farmacológico , Estudos RetrospectivosRESUMO
BACKGROUND: Postoperative pulmonary complications (PPCs) are associated with postoperative mortality and prolonged hospital stay. Although intraoperative mechanical ventilation (MV) is a risk factor for PPCs, strategies addressing weaning from MV are understudied. In this systematic review, we evaluated weaning strategies and their effects on postoperative pulmonary outcomes. METHODS: Our protocol was registered on PROSPERO (CRD42022379145). Eligible studies included randomised controlled trials and observational studies of adults weaned from MV in the operating room. Primary outcomes included atelectasis and oxygenation; secondary outcomes included lung volume changes and PPCs. Risk of bias was assessed using the Cochrane Risk of Bias (RoB2) tool, and quality of evidence with the GRADE framework. RESULTS: Screening identified 14 randomised controlled trials including 1719 patients; seven studies were limited to the weaning phase and seven included interventions not restricted to the weaning phase. Strategies combining pressure support ventilation (PSV) with positive end-expiratory pressure (PEEP) and low fraction of inspired oxygen (FiO2) improved atelectasis, oxygenation, and lung volumes. Low FiO2 improved atelectasis and oxygenation but might not improve lung volumes. A fixed-PEEP strategy led to no improvement in oxygenation or atelectasis; however, individualised PEEP with low FiO2 improved oxygenation and might be associated with reduced PPCs. Half of included studies are of moderate or high risk of bias; the overall quality of evidence is low. CONCLUSIONS: There is limited research evaluating weaning from intraoperative MV. Based on low-quality evidence, PSV, individualised PEEP, and low FiO2 may be associated with reduced postoperative pulmonary outcomes. SYSTEMATIC REVIEW PROTOCOL: PROSPERO (CRD42022379145).