Jonathan Millar

Extracorporeal carbon dioxide removal for patients with acute respiratory failure secondary to the acute respiratory distress syndrome: a systematic review

Acute respiratory distress syndrome (ARDS) continues to have significant mortality and morbidity. The only intervention proven to reduce mortality is the use of lung-protective mechanical ventilation strategies, although such a strategy may lead to problematic hypercapnia. Extracorporeal carbon dioxide removal (ECCO2R) devices allow uncoupling of ventilation from oxygenation, thereby removing carbon dioxide and facilitating lower tidal volume ventilation. We performed a systematic review to assess efficacy, complication rates, and utility of ECCO2R devices. We included randomised controlled trials (RCTs), case–control studies and case series with 10 or more patients. We searched MEDLINE, Embase, LILACS (Literatura Latino Americana em Ciências da Saúde), and ISI Web of Science, in addition to grey literature and clinical trials registries. Data were independently extracted by two reviewers against predefined criteria and agreement was reached by consensus. Outcomes of interest included mortality, intensive care and hospital lengths of stay, respiratory parameters and complications. The review included 14 studies with 495 patients (two RCTs and 12 observational studies). Arteriovenous ECCO2R was used in seven studies, and venovenous ECCO2R in seven studies. Available evidence suggests no mortality benefit to ECCO2R, although post hoc analysis of data from the most recent RCT showed an improvement in ventilator-free days in more severe ARDS. Organ failure-free days or ICU stay have not been shown to decrease with ECCO2R. Carbon dioxide removal was widely demonstrated as feasible, facilitating the use of lower tidal volume ventilation. Complication rates varied greatly across the included studies, representing technological advances. There was a general paucity of high-quality data and significant variation in both practice and technology used among studies, which confounded analysis. ECCO2R is a rapidly evolving technology and is an efficacious treatment to enable protective lung ventilation. Evidence for a positive effect on mortality and other important clinical outcomes is lacking. Rapid technological advances have led to major changes in these devices and together with variation in study design have limited applicability of analysis. Further well-designed adequately powered RCTs are needed.

The use of high-flow nasal oxygen therapy in the management of hypercarbic respiratory failure:

Hypercarbic respiratory failure, occurring secondary to chronic lung disease, is a frequently encountered problem. These patients present a significant challenge to respiratory and critical care services, as many are unsuitable for mechanical ventilation and most have multiple comorbidities. Recently, noninvasive ventilation (NIV) has become established as the primary modality for respiratory support in this group of patients. Several factors limit patient compliance with NIV, not least comfort and tolerability. A recent innovation in adult critical care is the use of high-flow nasal oxygen (HFNO) devices. These systems are capable of delivering high gas flows via nasal cannulae, with the ability to blend air and oxygen to give a controlled FiO2. Few clinical studies have been conducted in adults, although several are planned. To date the majority of available evidence addresses the use of HFNO in hypoxemic respiratory failure. Here we present a case in which a HFNO system was used to successfully manage hypercarbic respiratory failure in a patient unable to tolerate conventional NIV.

The inflammatory response to extracorporeal membrane oxygenation (ECMO): a review of the pathophysiology

Extracorporeal membrane oxygenation (ECMO) is a technology capable of providing short-term mechanical support to the heart, lungs or both. Over the last decade, the number of centres offering ECMO has grown rapidly. At the same time, the indications for its use have also been broadened. In part, this trend has been supported by advances in circuit design and in cannulation techniques. Despite the widespread adoption of extracorporeal life support techniques, the use of ECMO remains associated with significant morbidity and mortality. A complication witnessed during ECMO is the inflammatory response to extracorporeal circulation. This reaction shares similarities with the systemic inflammatory response syndrome (SIRS) and has been well-documented in relation to cardiopulmonary bypass. The exposure of a patient’s blood to the non-endothelialised surface of the ECMO circuit results in the widespread activation of the innate immune system; if unchecked this may result in inflammation and organ injury. Here, we review the pathophysiology of the inflammatory response to ECMO, highlighting the complex interactions between arms of the innate immune response, the endothelium and coagulation. An understanding of the processes involved may guide the design of therapies and strategies aimed at ameliorating inflammation during ECMO. Likewise, an appreciation of the potentially deleterious inflammatory effects of ECMO may assist those weighing the risks and benefits of therapy.

Administration of mesenchymal stem cells during ECMO results in a rapid decline in oxygenator performance

Mesenchymal stem cells (MSCs) have attracted attention as a potential therapy for Acute Respiratory Distress Syndrome (ARDS). At the same time, the use of extracorporeal membrane oxygenation (ECMO) has increased among patients with severe ARDS. To date, early clinical trials of MSCs in ARDS have excluded patients supported by ECMO. Here we provide evidence from an ex-vivo model of ECMO to suggest that the intravascular administration of MSCs during ECMO may adversely impact the function of a membrane oxygenator. The addition of clinical grade MSCs resulted in a reduction of flow through the circuit in comparison to controls (0.6 ±0.35 L min-1vs 4.12 ± 0.03 L min-1, at 240 minutes) and an increase in the transoygenator pressure gradient (101±9 mmHg vs 21±4 mmHg, at 240 minutes). Subsequent immunohistochemistry analysis demonstrated quantities of MSCs highly adherent to membrane oxygenator fibres. This study highlights the potential harm associated with MSC therapy during ECMO and suggests further areas of research required to advance the translation of cell therapy in this population.

Differential immunological profiles herald magnetic resonance imaging-defined perioperative cerebral infarction

Background: The perioperative period is associated with a high risk for human ischaemic stroke. Although inflammatory mechanisms are known to have an important role in cerebral infarction in the nonoperative setting, their role in modulating perioperative risk remains unclear. Methods: In this prospective case-control study, we compared 10 patients (cases) who developed magnetic resonance imaging (MRI) evidence of cerebral infarction following transcatheter aortic valve implantation with 10 patients (controls) who underwent the same procedure without neurological complication. Blood sampling was performed preoperatively (baseline) and at 24 h, 48 h and 72 h postoperatively and analysed for specific cytokines, chemokines and complement factors. Results: Baseline serum assessments identified significant differences between the two cohorts for levels of complement C3, complement C4b, granulocyte-macrophage colony-stimulating factor, interleukin-15 and macrophage inflammatory protein-1β. Longitudinal regression analysis and best-fit polynomial curves of postoperative analyte profiles identified significantly higher levels of complement C3 and matrix metalloproteinase-9, and lower levels of interferon-γ and macrophage inflammatory protein-1β levels in cases versus controls. Conclusions: These results support a potentially important role for inflammatory mechanisms in MRI-defined perioperative stroke and reveal a potentially important role for complement components in this process.

The past, present, and future

Mechanical circulatory and respiratory support (MCRS) therapies are now an established feature of modern medicine. Substantial progress has been made in the MCRS field during the last decade, much of it built upon pioneering work carried out since the 1950s. Increasingly, international registries are recording a rapid expansion in the number of patients supported with MCRS devices and in the number of centers capable of providing these interventions. Improved technologies now offer hope to patients who even recently would have died of their illnesses. Work continues to develop newer, more sophisticated devices that limit the adverse effects and improve performance. In this chapter, we look forward to identify areas which will be important in the future of MCRS. In doing so, we consider both the technological and organizational factors that will influence the continued development of the field.

The soda dipstick: A convenient and cost‐effective means of identifying the sugar content of soft drinks

The use of carbohydrate counting is a common means by which patients with type 1 diabetes mellitus may improve their glycemic control and has been shown to be efficacious in adults. Despite this, judging the carbohydrate content of meals and snacks is often difficult, with underestimation being associated with higher glycemic variability and a shorter time spent within the glycemic target range. A challenge to carbohydrate counting may be posed by the unknowing consumption of sugarsweetened soft drinks. The increasing consumption of soft drinks is a global phenomenon, with annual average worldwide consumption estimated at 45.1L (11.4 gallons) per person in 2010. In response to an increasing public awareness of the potential harms associated with soft drink consumption, many manufacturers have started to produce low-sugar or sugar-free alternatives. Although the sugar content of drinks is usually made clear by producers, and in fact often used to promote a product, in social circumstances drinks packaging may not be readily available. In addition, previous investigation has shown that distinguishing sugar-sweetened from sugar-free products by taste is inaccurate. Reagent test strips (or dipsticks) are routinely used to identify the presence of glucose in urine. The presence of glucose in solution is indicated by a color change on the test strip, which requires no advanced knowledge or training to recognize. These strips are of low cost and are easily stored with a long shelf life. We investigated the ability of urine test strips to distinguish between sugar-free and sugar-sweetened soft drinks. Commercially available urine test strips (Combur; Roche Diagnostics, Rotkreuz, Switzerland) were used to test four common soft drinks for the presence of glucose: Coca-Cola, Diet Coca-Cola, Sprite and Sprite Zero (The Coca-Cola Company, Atlanta, GA, USA). The sugar content for each beverage was retrieved from the manufacturer’s website (http://www.coca-cola.co.uk/drinks/cocacola/, accessed 11 May 2016). Diet Coca-Cola and Sprite Zero were reported as being sugar free, whereas Coca-Cola contains 10.6g/dL sugar and Sprite contains 6.6g/dL sugar. Two investigators, blinded to the identity of the beverages, conducted the experiments. Beverages were obtained from 2-L containers of cola, diet cola, clear diet soda or clear soda and, from each, 20 50-mL samples were decanted into polystyrene cups. Each sample was tested using the test strips as per the manufacturer’s instructions, as if urine was being analyzed. The presence or absence of glucose was noted. Urine test strips showed strongly positive for glucose in all 40 sugar-containing samples. Equally, test strips remained unequivocally negative for glucose in all 40 sugar-free samples. Results were clear within 60 s in all tests. This investigation demonstrates that urine test strips are a convenient, cheap, and accurate means of differentiating sugar-sweetened from sugar-free soft drinks. However, there are several limitations to the present study. First, urine dipsticks only test for the presence of glucose. Many soft drinks also contain sugar as fructose or sucrose, which would not be detected by these strips. Second, we did not formally assess whether the use of the test strips adversely altered the flavor or safety of the beverage, and therefore recommend that drinks should only be tested by obtaining small aliquots that are subsequently discarded. Given the global soft drink variety and consumption, patients with type 1 diabetes who rely on carbohydrate counting to enhance glycemic control require an easy means of avoiding inadvertent sugar consumption. The use of urine test strips, easily available, may provide a practical means of identification.

Need for systematic audit of trauma care in Northern Ireland.

The 2016 budget gave the NHS in Northern Ireland a small amount of new funding.1 We like many others were delighted to hear the announcement, by the chancellor and the minister of health at the Northern Ireland Assembly, of funding for a helicopter emergency medical service (HEMS). …