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2.
Perfusion ; 35(1_suppl): 38-49, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32397884

RESUMO

With ongoing progress of components of extracorporeal membrane oxygenation including improvements of oxygenators, pumps, and coating materials, extracorporeal membrane oxygenation became increasingly accepted in the clinical practice. A suitable testing in an adequate setup is essential for the development of new technical aspects. Relevant tests can be conducted in ex vivo models specifically designed to test certain aspects. Different setups have been used in the past for specific research questions. We conducted a systematic literature review of ex vivo models of extracorporeal membrane oxygenation components. MEDLINE and Embase were searched between January 1996 and October 2017. The inclusion criteria were ex vivo models including features of extracorporeal membrane oxygenation technology. The exclusion criteria were clinical studies, abstracts, studies in which the model of extracorporeal membrane oxygenation has been reported previously, and studies not reporting on extracorporeal membrane oxygenation components. A total of 50 studies reporting on different ex vivo extracorporeal membrane oxygenation models have been identified from the literature search. Models have been grouped according to the specific research question they were designed to test for. The groups are focused on oxygenator performance, pump performance, hemostasis, and pharmacokinetics. Pre-clinical testing including use of ex vivo models is an important step in the development and improvement of extracorporeal membrane oxygenation components and materials. Furthermore, ex vivo models offer valuable insights for clinicians to better understand the consequences of choice of components, setup, and management of an extracorporeal membrane oxygenation circuit in any given condition. There is a need to standardize the reporting of pre-clinical studies in this area and to develop best practice in their design.

3.
Arch Dis Child ; 2020 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-32276987

RESUMO

BACKGROUND: Bronchiolitis is the most common reason for hospital admission in infants. High-flow oxygen therapy has emerged as a new treatment; however, the cost-effectiveness of using it as first-line therapy is unknown. OBJECTIVE: To compare the cost of providing high-flow therapy as a first-line therapy compared with rescue therapy after failure of standard oxygen in the management of bronchiolitis. METHODS: A within-trial economic evaluation from the health service perspective using data from a multicentre randomised controlled trial for hypoxic infants (≤12 months) admitted to hospital with bronchiolitis in Australia and New Zealand. Intervention costs, length of hospital and intensive care stay and associated costs were compared for infants who received first-line treatment with high-flow therapy (early high-flow, n=739) or for infants who received standard oxygen and optional rescue high-flow (rescue high-flow, n=733). Costs were applied using Australian costing sources and are reported in 2016-2017 AU$. RESULTS: The incremental cost to avoid one treatment failure was AU$1778 (95% credible interval (CrI) 207 to 7096). Mean cost of bronchiolitis treatment including intervention costs and costs associated with length of stay was AU$420 (95% CrI -176 to 1002) higher per infant in the early high-flow group compared with the rescue high-flow group. There was an 8% (95% CrI 7.5 to 8.6) likelihood of the early high-flow oxygen therapy being cost saving. CONCLUSIONS: The use of high-flow oxygen as initial therapy for respiratory failure in infants with bronchiolitis is unlikely to be cost saving to the health system, compared with standard oxygen therapy with rescue high-flow.

6.
Artigo em Inglês | MEDLINE | ID: mdl-32293914

RESUMO

RATIONALE: Mesenchymal stromal cell therapy is a promising intervention for ARDS, although trials to date have not investigated its use alongside ECMO. Recent pre-clinical studies have suggested that combining these interventions may attenuate the efficacy of ECMO. OBJECTIVES: To determine the safety and efficacy of mesenchymal stromal cell therapy in a model of ARDS and ECMO. METHODS: ARDS was induced in 14 sheep, after which they were established on veno-venous ECMO. Subsequently, they received either, endobronchial iPSC-derived human MSCs (hMSCs, n=7) or cell-free carrier vehicle (Vehicle control, n=7). During ECMO, a low tidal volume ventilation strategy was employed in addition to protocolized hemodynamic support. Animals were monitored and supported for 24 hours. Lung tissue, bronchoalveolar fluid, and plasma were analysed, in addition to continuous respiratory and hemodynamic monitoring. MEASUREMENTS AND MAIN RESULTS: The administration of hMSCs did not improve oxygenation (PaO2/FiO2 mean difference -146 mmHg, p = 0.076) or pulmonary function. However, histological evidence of lung injury (Lung Injury Score mean difference -0.07, p = 0.04) and BAL IL-8 were reduced. In addition, hMSC treated animals had a significantly lower cumulative requirement for vasopressor. Despite endobronchial administration, animals treated with hMSCs had a significant elevation in trans-membrane oxygenator pressure gradients. This was accompanied by more pulmonary artery thromboses and adherent hMSCs found on explanted oxygenator fibers. CONCLUSIONS: Endobronchial hMSC therapy in an ovine model of ARDS and ECMO can impair membrane oxygenator function and does not improve oxygenation. These data do not recommend the safe use of hMSCs during VV-ECMO.

7.
Aust Crit Care ; 33(3): 213-218, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32299649

RESUMO

BACKGROUND: Conjecture remains regarding the optimal timing for tracheostomy. Most studies examine patient mortality, ventilation duration, intensive care unit (ICU) length of stay, and medical complications. Few studies examine patient-centric outcomes. The aim of this study was to determine whether timing of tracheostomy had an impact on length of stay, morbidity, mortality, and patient-centric outcomes towards their functional recovery. METHODS: This prospective observational study included data for all tracheostomised patients over 4 y in a tertiary ICU. The study time period commenced with the insertion of an endotracheal tube. Data collected included patient and disease specifics; mortality up to 4 y; mobility scores; and time to oral intake, talking, and out-of-bed exercises. To assess differences between timing of tracheostomy, a survival analysis was conducted to dynamically compare patients on days before and after tracheostomy tube (TT) placement during their ICU admission. RESULTS: TT was placed in 276 patients. After tracheostomy, the patients were able to (on average) verbally communicate 7.4 d earlier (confidence interval [CI] = -9.1 to -4.9), return to oral intake 7.0 d earlier (CI = -10 to -4.6), and perform out-of-bed exercises 6.2 d earlier (CI = -8.4 to -4) than those who did not yet have a TT. In patients with an endotracheal tube, none were able to talk or have oral intake, and the majority (99%) did not participate in out-of-bed exercises/active rehabilitation. After tracheostomy, patients subsequently received significantly less analgesic and sedative drugs and more antipsychotics. No clear differences in ICU and long-term mortality were associated with tracheostomy timing. CONCLUSIONS: Earlier tracheostomy is associated with earlier achievement of patient-centric outcomes - patients returning to usual daily activities such as talking, out-of-bed mobility, and eating/drinking significantly earlier, whilst also receiving less sedatives and analgesics.

8.
J Cell Mol Med ; 24(8): 4791-4803, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32180339

RESUMO

Coronary artery bypass grafting (CABG) triggers a systemic inflammatory response that may contribute to adverse outcomes. Dendritic cells (DC) and monocytes are immunoregulatory cells potentially affected by CABG, contributing to an altered immune state. This study investigated changes in DC and monocyte responses in CABG patients at 5 time-points: admission, peri-operative, ICU, day 3 and day 5. Whole blood from 49 CABG patients was used in an ex vivo whole blood culture model to prospectively assess DC and monocyte responses. Lipopolysaccharide (LPS) was added in parallel to model responses to an infectious complication. Co-stimulatory and adhesion molecule expression and intracellular mediator production was measured by flow cytometry. CABG modulated monocyte and DC responses. In addition, DC and monocytes were immunoparalysed, evidenced by failure of co-stimulatory and adhesion molecules (eg HLA-DR), and intracellular mediators (eg IL-6) to respond to LPS stimulation. DC and monocyte modulation was associated with prolonged ICU length of stay and post-operative atrial fibrillation. DC and monocyte cytokine production did not recover by day 5 post-surgery. This study provides evidence that CABG modulates DC and monocyte responses. Using an ex vivo model to assess immune competency of CABG patients may help identify biomarkers to predict adverse outcomes.

9.
Crit Care Med ; 48(4): e332, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32205624
10.
Transplantation ; 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32150037

RESUMO

Despite advances in mechanical circulatory devices and pharmacological therapies, heart transplantation is the definitive and most effective therapy for an important proportion of qualifying patients with end-stage heart failure. However, the demand for donor hearts significantly outweighs the supply. Hearts are sourced from donors following brain death, which exposes donor hearts to substantial pathophysiological perturbations that can influence heart transplant success and recipient survival. While significant advances in recipient selection, donor and HTx recipient management, immunosuppression and pretransplant mechanical circulatory support have been achieved, primary graft dysfunction after cardiac transplantation continues to be an important cause of morbidity and mortality.Animal models, when appropriate, can guide/inform medical practice, and fill gaps in knowledge that are unattainable in clinical settings. Consequently, we performed a systematic review of existing animal models that incorporate donor brain death and subsequent heart transplantation, and assessed studies for scientific rigor and clinical relevance. Following literature screening via MEDLINE and Embase, 29 studies were assessed. Analysis of included studies identified marked heterogeneity in animal models of donor brain death coupled to heart transplantation, with few research groups worldwide identified as utilizing these models. General reporting of important determinants of heart transplant success was mixed, and assessment of posttransplant cardiac function was limited to an invasive technique (pressure-volume analysis), which is limitedly applied in clinical settings.This review highlights translational challenges between available animal models and clinical heart transplant settings that is potentially hindering advancement of this field of investigation.

11.
Artigo em Inglês | MEDLINE | ID: mdl-32043304

RESUMO

AIM: Nasal high-flow oxygen therapy is increasingly used in infants for supportive respiratory therapy in bronchiolitis. It is unclear whether enteral hydration is safe in children receiving high-flow. METHODS: We performed a planned secondary analysis of a multi-centre, randomised controlled trial of infants aged <12 months with bronchiolitis and an oxygen requirement. Children were assigned to treatment with either high-flow or standard-oxygen therapy with optional rescue high-flow. We assessed adverse events based on how children on high-flow were hydrated: intravenously (IV), via bolus or continuous nasogastric tube (NGT) or orally. RESULTS: A total of 505 patients on high-flow via primary study assignment (n = 408), primary treatment (n = 10) or as rescue therapy (n = 87) were assessed. While on high flow, 15 of 505 (3.0%) received only IV fluids, 360 (71.3%) received only enteral fluids and 93 (18.4%) received both IV and enteral fluids. The route was unknown in 37 (7.3%). Of the 453 high-flow infants hydrated enterally patients could receive one or more methods of hydration; 80 (15.8%) received NGT bolus, 217 (43.0%) NGT continuous, 118 (23.4%) both bolus and continuous, 32 (6.3%) received only oral hydration and 171 (33.9%) a mix of NGT and oral hydration. None of the patients receiving oral or NGT hydration on high-flow sustained pulmonary aspiration (0%; 95% confidence interval N/A); one patient had a pneumothorax (0.2%; 95% confidence interval 0.0-0.7%). CONCLUSIONS: The vast majority of children with hypoxic respiratory failure in bronchiolitis can be safely hydrated enterally during the period when they receive high-flow.

12.
Emerg Med Australas ; 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32043315

RESUMO

OBJECTIVES: To describe haemodynamic resuscitation practices in ED patients with suspected sepsis and hypotension. METHODS: This was a prospective, multicentre, observational study conducted in 70 hospitals in Australia and New Zealand between September 2018 and January 2019. Consecutive adults presenting to the ED during a 30-day period at each site, with suspected sepsis and hypotension (systolic blood pressure <100 mmHg) despite at least 1000 mL fluid resuscitation, were eligible. Data included baseline demographics, clinical and laboratory variables and intravenous fluid volume administered, vasopressor administration at baseline and 6- and 24-h post-enrolment, time to antimicrobial administration, intensive care admission, organ support and in-hospital mortality. RESULTS: A total of 4477 patients were screened and 591 were included with a mean (standard deviation) age of 62 (19) years, Acute Physiology and Chronic Health Evaluation II score 15.2 (6.6) and a median (interquartile range) systolic blood pressure of 94 mmHg (87-100). Median time to first intravenous antimicrobials was 77 min (42-148). A vasopressor infusion was commenced within 24 h in 177 (30.2%) patients, with noradrenaline the most frequently used (n = 138, 78%). A median of 2000 mL (1500-3000) of intravenous fluids was administered prior to commencing vasopressors. The total volume of fluid administered from pre-enrolment to 24 h was 4200 mL (3000-5661), with a range from 1000 to 12 200 mL. Two hundred and eighteen patients (37.1%) were admitted to an intensive care unit. Overall in-hospital mortality was 6.2% (95% confidence interval 4.4-8.5%). CONCLUSION: Current resuscitation practice in patients with sepsis and hypotension varies widely and occupies the spectrum between a restricted volume/earlier vasopressor and liberal fluid/later vasopressor strategy.

13.
Artif Organs ; 44(6): E238-E250, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31951020

RESUMO

Controlled and repeatable in vitro evaluation of cardiovascular devices using a mock circulation loop (MCL) is essential prior to in vivo or clinical trials. MCLs often consist of only a systemic circulation with no autoregulatory responses and limited validation. This study aimed to develop, and validate against human data, an advanced MCL with systemic, pulmonary, cerebral, and coronary circulations with autoregulatory responses. The biventricular MCL was constructed with pneumatically controlled hydraulic circulations with Starling responsive ventricles and autoregulatory cerebral and coronary circulations. Hemodynamic repeatability was assessed and complemented by validation using impedance cardiography data from 50 healthy humans. The MCL successfully simulated patient scenarios including rest, exercise, and left heart failure with and without cardiovascular device support. End-systolic pressure-volume relationships for respective healthy and heart failure conditions had slopes of 1.27 and 0.54 mm Hg mL-1 (left ventricle), and 0.18 and 0.10 mm Hg mL-1 (right ventricle), aligning with the literature. Coronary and cerebral autoregulation showed a strong correlation (R2 : .99) between theoretical and experimentally derived circuit flow. MCL repeatability was demonstrated with correlation coefficients being statistically significant (P < .05) for all simulated conditions while MCL hemodynamics aligned well with human data. This advanced MCL is a valuable tool for inexpensive and controlled evaluation of cardiovascular devices.

14.
Artif Organs ; 44(3): E40-E53, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31520408

RESUMO

Due to improved durability and survival rates, rotary blood pumps (RBPs) are the preferred left ventricular assist device when compared to volume displacement pumps. However, when operated at constant speed, RBPs lack a volume balancing mechanism which may result in left ventricular suction and suboptimal ventricular unloading. Starling-like controllers have previously been developed to balance circulatory volumes; however, they do not consider ventricular workload as a feedback and may have limited sensitivity to adjust RBP workload when ventricular function deteriorates or improves. To address this, we aimed to develop a Starling-like total work controller (SL-TWC) that matched the energy output of a healthy heart by adjusting RBP hydraulic work based on measured left ventricular stroke work and ventricular preload. In a mock circulatory loop, the SL-TWC was evaluated using a HeartWare HVAD in a range of simulated patient conditions. These conditions included changes in systemic hypertension and hypotension, pulmonary hypertension, blood circulatory volume, exercise, and improvement and deterioration of ventricular function by increasing and decreasing ventricular contractility. The SL-TWC was compared to constant speed control where RBP speed was set to restore cardiac output to 5.0 L/min at rest. Left ventricular suction occurred with constant speed control during pulmonary hypertension but was prevented with the SL-TWC. During simulated exercise, the SL-TWC demonstrated reduced LVSW (0.51 J) and greater RBP flow (9.2 L/min) compared to constant speed control (LVSW: 0.74 J and RBP flow: 6.4 L/min). In instances of increased ventricular contractility, the SL-TWC reduced RBP hydraulic work while maintaining cardiac output similar to the rest condition. In comparison, constant speed overworked and increased cardiac output. The SL-TWC balanced circulatory volumes by mimicking the Starling mechanism, while also considering changes in ventricular workload. Compared to constant speed control, the SL-TWC may reduce complications associated with volume imbalances, adapt to changes in ventricular function and improve patient quality of life.

16.
BMJ Open ; 9(12): e030516, 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31857300

RESUMO

INTRODUCTION: Acute hypoxaemic respiratory failure (AHRF) in children is the most frequent reason for non-elective hospital admission. During the initial phase, AHRF is a clinical syndrome defined for the purpose of this study by an oxygen requirement and caused by pneumonia, lower respiratory tract infections, asthma or bronchiolitis. Up to 20% of these children with AHRF can rapidly deteriorate requiring non-invasive or invasive ventilation. Nasal high-flow (NHF) therapy has been used by clinicians for oxygen therapy outside intensive care settings to prevent escalation of care. A recent randomised trial in infants with bronchiolitis has shown that NHF therapy reduces the need to escalate therapy. No similar data is available in the older children presenting with AHRF. In this study we aim to investigate in children aged 1 to 4 years presenting with AHRF if early NHF therapy compared with standard-oxygen therapy reduces hospital length of stay and if this is cost-effective compared with standard treatment. METHODS AND ANALYSIS: The study design is an open-labelled randomised multicentre trial comparing early NHF and standard-oxygen therapy and will be stratified by sites and into obstructive and non-obstructive groups. Children aged 1 to 4 years (n=1512) presenting with AHRF to one of the participating emergency departments will be randomly allocated to NHF or standard-oxygen therapy once the eligibility criteria have been met (oxygen requirement with transcutaneous saturation <92%/90% (dependant on hospital standard threshold), diagnosis of AHRF, admission to hospital and tachypnoea ≥35 breaths/min). Children in the standard-oxygen group can receive rescue NHF therapy if escalation is required. The primary outcome is hospital length of stay. Secondary outcomes will include length of oxygen therapy, proportion of intensive care admissions, healthcare resource utilisation and associated costs. Analyses will be conducted on an intention-to-treat basis. ETHICS AND DISSEMINATION: Ethics approval has been obtained in Australia (HREC/15/QRCH/159) and New Zealand (HDEC 17/NTA/135). The trial commenced recruitment in December 2017. The study findings will be submitted for publication in a peer-reviewed journal and presented at relevant conferences. Authorship of all publications will be decided by mutual consensus of the research team. TRIAL REGISTRATION NUMBER: ACTRN12618000210279.

17.
PLoS One ; 14(12): e0227248, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31887197

RESUMO

Effective and safe practices during extracorporeal membrane oxygenation (ECMO) including infection precautions and securement of lines (cannulas and circuits) are critical to prevent life-threatening patient complications, yet little is known about the practices of bedside clinicians and data to support best practice is lacking. Therefore, the aim of this study was to identify and describe common line-related practices for patients supported by peripheral ECMO worldwide and to highlight any gaps for further investigation. An electronic survey was conducted to examine common line practices for patients managed on peripheral ECMO. Responses were obtained from 45 countries with the majority from the United States (n = 181) and United Kingdom (n = 32). Standardised infection precautions including hand hygiene, maximal barrier precautions and skin antisepsis were commonplace for cannulation. The most common antisepsis strategies included alcohol-based chlorhexidine gluconate (CHG) for cannula insertion (53%) and maintenance (54%), isopropyl alcohol on circuit access ports (39%), and CHG-impregnated dressings to cover insertion sites (36%). Adverse patient events due to line malposition or dislodgement were reported by 34% of respondents with most attributable to ineffective securement. Centres 'always' suturing peripheral cannula sites were more likely to experience a cannula adverse event than centres that 'never' sutured (35% [95% CI 30, 41] vs 0% [95% CI 0, 28]; Chi-square 4.40; p = 0.04) but this did not meet the a priori significance level of <0.01. An evidence-based guideline would be beneficial to improve ECMO line management according to 78% of respondents. Evidence gaps were identified for antiseptic agents, dressing products and regimens, securement methods, and needleless valves. Future research addressing these areas may provide opportunities for consensus guideline development and practice improvement.


Assuntos
Cânula/efeitos adversos , Infecções Relacionadas a Cateter/prevenção & controle , Cateterismo Periférico/efeitos adversos , Oxigenação por Membrana Extracorpórea/efeitos adversos , Padrões de Prática Médica/estatística & dados numéricos , Anti-Infecciosos Locais/administração & dosagem , Cânula/microbiologia , Infecções Relacionadas a Cateter/etiologia , Cateterismo Periférico/instrumentação , Cateterismo Periférico/normas , Desinfetantes/administração & dosagem , Desinfecção/métodos , Desinfecção/estatística & dados numéricos , Oxigenação por Membrana Extracorpórea/instrumentação , Oxigenação por Membrana Extracorpórea/normas , Fidelidade a Diretrizes/estatística & dados numéricos , Higiene das Mãos/estatística & dados numéricos , Humanos , Guias de Prática Clínica como Assunto , Padrões de Prática Médica/normas , Inquéritos e Questionários/estatística & dados numéricos
18.
Front Pediatr ; 7: 426, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31709201

RESUMO

Background: Bronchiolitis is the most common reason for hospital admission in infants, with one third requiring oxygen therapy due to hypoxemia. It is unknown what proportion of hypoxemic infants with bronchiolitis can be managed with nasal high-flow in room air and their resulting outcomes. Objectives and Settings: To assess the effect of nasal high-flow in room air in a subgroup of infants with bronchiolitis allocated to high-flow therapy in a recent multicenter randomized controlled trial. Patients and Interventions: Infants allocated to the high-flow arm of the trial were initially treated with room air high-flow if saturations were ≥85%. Subsequently, if oxygen saturations did not increase to ≥92%, oxygen was added and FiO2 was titrated to increase the oxygen saturations. In this planned sub-study, infants treated during their entire hospital stay with high-flow room air only were compared to infants receiving either standard-oxygen or high-flow with oxygen. Baseline characteristics, hospital length of stay and length of oxygen therapy were compared. Findings: In the per protocol analysis 64 (10%) of 630 infants commenced on high-flow room air remained in room air only during the entire stay in hospital. These infants on high-flow room air were on average older and presented with moderate hypoxemia at presentation to hospital. Their length of respiratory support and length of stay was also significantly shorter. No pre-enrolment factors could be identified in a multivariable analysis. Conclusions: In a small sub-group of hypoxemic infants with bronchiolitis hypoxemia can be reversed with the application of high-flow in room air only. Trial registration: ACTRN12615001305516.

19.
Aust Crit Care ; 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31495639

RESUMO

The publisher regrets that this article has been temporarily removed. A replacement will appear as soon as possible in which the reason for the removal of the article will be specified, or the article will be reinstated. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

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