Yoke Fung - Academia.edu (original) (raw)

Papers by Yoke Fung

Research paper thumbnail of The Sheep as a Transfusion Model: Comparison of the Storage Lesion of Human and Ovine Red Blood Cell Units

Transfusion Medicine, 2013

Introduction: There is growing awareness of risks related to transfusion of stored blood products... more Introduction: There is growing awareness of risks related to transfusion of stored blood products. Animal models (e.g. ovine) will bevital to investigating the underlying mechanisms. This study aimed to characterise specific aspects of the storage lesion of ovine (ov) packed red blood cell (PRBC) units and compare these to equivalent human PRBC (huPRBC) units, expanding upon our previous reports of biochemical changes and haemolysis rates. Methods: Whole blood was collected from adult Merino ewes (n=5) into blood packs containing citrate-phosphate-dextrose (CPD) and processed into leucodepleted ovPRBCs preserved in saline, adenine, glucose and mannitol (SAGM) additive solution. Equivalent huPRBCs (n=5) were provided by the Australian Red Cross Blood Service. OvPRBCs and huPRBCs were stored at 2-6 ◦ C for 42 days, and samples were collected aseptically at weekly intervals (days 1, 7, 14, 21, 28, 35 and 42). Samples underwent testing for 2,3-diphosphoglycerate (2,3- DPG) and adenosine...

Research paper thumbnail of Sheep red blood cells for transfusion: is the storage lesion comparable to human red blood cells?

Research paper thumbnail of Primary immunodeficiency disease: a cost-utility analysis comparing intravenous vs subcutaneous immunoglobulin replacement therapy in Australia

BACKGROUND Hospital-based intravenous immunoglobulin (IVIg) treatment has been the standard treat... more BACKGROUND Hospital-based intravenous immunoglobulin (IVIg) treatment has been the standard treatment mode for patients with primary immunodeficiency disease (PID). With the newer home-based subcutaneous immunoglobulin (SCIg) becoming approved for use in most countries, the question arises as to whether SCIg is a cost-effective treatment mode compared to IVIg in Australia. MATERIALS AND METHODS We developed a Markov cohort simulation model with six health states: PID without infection, PID with infection treated at home or hospital, bronchiectasis without infection, bronchiectasis with infection treated at home or hospital, bronchiectasis with chronic Pseudomonas aeruginosa infection, and death, from an Australian healthcare system perspective. A 10-year time horizon with weekly cycles was chosen, and the expected costs and quality-adjusted life-years (QALYs) of the two treatment options estimated. RESULTS The cumulative 10-year cost per patient was 297,547 Australian dollars (A$) w...

Research paper thumbnail of Unplanned blood use within 24 hours of emergency department presentation: A cohort study in an ageing population

Emergency Medicine Australasia

OBJECTIVE This research aims to elucidate drivers of blood use in an older population, with a foc... more OBJECTIVE This research aims to elucidate drivers of blood use in an older population, with a focus on unplanned transfusions following ED presentation. METHODS In a retrospective cohort study we examined 2015 data for ED presentations and blood use in two hospitals serving a population containing a high proportion (21%) of adults aged ≥65 years. Unplanned blood use was defined as any transfusion ≤24 h of presentation. Data were analysed by age, sex, Major Diagnostic Category, triage category and time to transfusion. RESULTS A total of 5294 blood components were transfused, comprising red cells (n = 3784), fresh frozen plasma (n = 657), platelets (n = 563) and cryoprecipitate (n = 290). Men aged ≥65 years were the highest users (40%, 2107 components). Unplanned transfusions accounted for 28% (n = 1057) of annual red cell use. Of 85 014 ED presentations, 494 (0.6%) were associated with unplanned red cell transfusion. Four Major Diagnostic Categories accounted for 81% (n = 853) of unplanned red cell use: gastrointestinal (n = 375), haematology (n = 267), trauma (n = 144) and cardiovascular (n = 67). Over one-fifth of unplanned transfusions (21%, n = 222 of 1057) were associated with ICD-10 codes for anaemia as a reason for presentation within the Haematology Major Diagnostic Category. Adults aged ≥65 years accounted for 62% of overall red cell use and 61% of transfusions ≤24 h of presentation. Odds of unplanned red cell transfusion increased with age, peaking at odds ratio 28.5 (95% confidence interval 14.2-57.4) in those aged 85 years and above. CONCLUSIONS Unplanned blood use accounted for 28% of annual hospital blood consumption. Blood component use increased with age and was greatest in older men. A significant burden of anaemia treatment was identified by the ED.

Research paper thumbnail of Research Article – BMC Health Service Research (IF -1.93) Barriers and Facilitators to Implementing Evidence Based Bleeding Management in Australian Cardiac Surgery Units: A Qualitative Interview Study Analysed With the Theoretical Domains Framework and COM-B Model

BackgroundBleeding during cardiac surgery is a common complication that often requires the transf... more BackgroundBleeding during cardiac surgery is a common complication that often requires the transfusion of blood products. The combination of bleeding and blood product transfusion incrementally increases adverse outcomes including infection and mortality. Following bleeding management guideline recommendationscould assist with minimising risk but adherence is not high, and the cause for lack of adherence is not well understood. This study aimed to identify barriers and facilitators to practicing and implementing evidenced-based bleeding management in Australian cardiac surgery units. MethodsWe used a qualitative descriptive design to conduct semi-structuredinterviews with Australian cardiac surgeons, anaesthetists and perfusionists.The Theoretical Domains Framework (TDF) was utilised toguide interviews and thematically analyse the data. Categorised data were then linkedwith the three key domains of the COM-B model (capability, opportunity, and motivation) to explore and understand b...

Research paper thumbnail of Barriers and Facilitators to Implementing Evidence Based Bleeding Management in Australian Cardiac Surgery Units: A Qualitative Interview study analysed with the Theoretical Domains Framework and COM-B model

BackgroundBleeding during cardiac surgery is a common complication that often requires the transf... more BackgroundBleeding during cardiac surgery is a common complication that often requires the transfusion of blood products. The combination of bleeding and blood product transfusion incrementally increases adverse outcomes including infection and mortality. Following bleeding management guideline recommendations could assist with minimising risk but adherence is not high, and the cause for lack of adherence is not well understood. This study aimed to identify barriers and facilitators to practicing and implementing evidenced-based intra-operative, bleeding management in Australian cardiac surgery units. MethodsWe used a qualitative descriptive design to conduct semi-structured interviews with Australian cardiac surgeons, anaesthetists and perfusionists. The Theoretical Domains Framework (TDF) was utilised to guide interviews and thematically analyse the data. Categorised data were then linked with the three key domains of the COM-B model (capability, opportunity, and motivation) to ex...

Research paper thumbnail of Bleeding Management Practices of Australian Cardiac Surgeons, Anesthesiologists and Perfusionists: A Cross-Sectional National Survey Incorporating the Theoretical Domains Framework (TDF) and COM-B Model

Journal of Multidisciplinary Healthcare

Purpose: Excessive bleeding is an acknowledged consequence of cardiac surgery, occurring in up to... more Purpose: Excessive bleeding is an acknowledged consequence of cardiac surgery, occurring in up to 10% of adult patients. This clinically important complication leads to poorer patient outcomes. Clinical practice guidelines are available to support best practice however variability in bleeding management practice and related adverse outcomes still exist. This study had two objectives: 1) to gain insight into current bleeding management practice for adult cardiac surgery in Australia and how that compared to guidelines and literature; and 2) to understand perceived difficulties clinicians face implementing improvements in bleeding management. Methods: A national cross-sectional questionnaire survey was utilized. Perspectives were sought from cardiac surgeons, cardiac anesthesiologists and perfusionists. Thirty-nine closedended questions focused on routine bleeding management practices to address pre and intraoperative care. One open-ended question was asked; "What would assist you to improve bleeding management with cardiac surgery patients?" Quantitative data were analysed with SPSS. Qualitative data were categorized into the domains of the Theoretical Domains Framework; the domains were then mapped to the COMB model. Results: Survey responses from 159 Anesthesiologists, 39 cardiac surgeons and 86 perfusionists were included (response rate 37%). Four of the recommendations queried in this survey were reported as routinely adhered to < 50% of the time, 9 queried recommendations were adhered to 51-75% of the time and 4 recommendations were routinely followed >76% of the time. Conclusion: There is a wide variation in peri-operative bleeding management practice among cardiac anaesthesiologists, surgeons and perfusionists in Australian cardiac surgery units. Conceptualizing factors believed necessary to improve practice with the TDF and COMB model found that bleeding management could be improved with a standardized approach including; point of care diagnostic assays, a bleeding management algorithm, access to concentrated coagulation factors, cardiac surgery specific bleeding management education, multidisciplinary team agreement and support, and an overarching national approach.

Research paper thumbnail of Dissimilar Respiratory and Hemodynamic Responses In TRALI Induced by Stored Red Cells and Whole Blood Platelets

Blood

1112 Background & Aims: Transfusion-related acute lung injury (TRALI) is a predominant cause of t... more 1112 Background & Aims: Transfusion-related acute lung injury (TRALI) is a predominant cause of transfusion-related morbidity and mortality, however the mechanism underlying its development remains undefined. We have previously demonstrated that heat-treated supernatant from stored (day 5) human whole blood platelet components (d5-PLT-S/N) cause TRALI in lipopolysaccharide (LPS) treated sheep (Tung et al. Vox Sang 2010). This two-event in-vivo model was used to further investigate TRALI due to heat-treated supernatant from stored (day 42) human red cells (d42-PRBC-S/N), and a comparison of the two models is reported here. Methods: Sheep were infused with LPS (15μg/kg; to model a first event of clinical infection), and then transfused with either d5-WB-PLT-S/N or d42-PRBC-S/N (10% of estimated blood volume; second event), with saline and supernatant from fresh blood components as controls. Microarray techniques were used to analyze cytokine and chemokine expression levels in both the...

Research paper thumbnail of Recipient T and B Lymphocytes Dictate the Severity of Antibody-Mediated Transfusion-Related Acute Lung Injury (TRALI)

Blood

641 Transfusion-related acute lung injury (TRALI) is a serious complication of transfusion and ha... more 641 Transfusion-related acute lung injury (TRALI) is a serious complication of transfusion and has been ranked as the leading cause of transfusion-related fatalities. The majority (approx. 80%) of TRALI reactions are associated with and probably initiated by donor alloantibodies recognizing recipient granulocytes and/or human leukocytes antigens (HLA). Nonetheless, many details of the immunopathogenesis of TRALI are unknown. Previous studies have shown that a murine anti-MHC (H-2Kd) class I antibody (clone 34-1-2s) can induce TRALI in mice (Looney et al J Clin Invest. 116:1615,2006) and we utilized this model in an attempt to understand the role that recipient lymphocytes might play in TRALI reactions. BALB/c (H-2d) mice were injected iv with titrations of 34-1-2s and body temperature, morbidity/mortality, pulmonary granulocyte accumulation and serum levels of MIP-2 (the murine analog of human neutrophil chemokine IL8) were measured at various time points. Results showed that when B...

Research paper thumbnail of Impacts of Aging on Anemia Tolerance, Transfusion Thresholds, and Patient Blood Management

Transfusion Medicine Reviews

Evidence-based patient blood management guidelines commonly recommend restrictive hemoglobin thre... more Evidence-based patient blood management guidelines commonly recommend restrictive hemoglobin thresholds of 70 to 80 g/L for asymptomatic adults. However, most transfusion trials have enrolled adults across a broad age span, with few exclusive to older adults. Our recent meta-analysis of transfusion trials that focused on older adults paradoxically found lower mortality and fewer cardiac complications when these patients were managed using higher hemoglobin thresholds. We postulate that declining cardiac output with age contributes to deteriorating oxygen delivery capacity which impacts anemia-associated outcomes in older adults and propose a model to explain this age-related difference. We reviewed evidence concerning the pathophysiology of aging to explore the disparity in transfusion trial outcomes related to hemoglobin thresholds in different age groups. The literature was searched for normative cardiac output values at different ages in healthy adults. Using normative peak cardiac output data, we modeled oxygen delivery capacity in young, middle-aged, and older adults at a range of hemoglobin levels. Cardiovascular and pulmonary systems are impacted by age-related pathophysiological changes. Diminishing peak cardiac output associated with aging reduces the maximal oxygen delivery achievable under metabolic stress. Hence, at low hemoglobin levels, older adults are more susceptible to tissue hypoxia than younger adults. Our model predicts that an older adult with a hemoglobin of 100 g/L has a similar peak oxygen delivery capacity to a young adult with a hemoglobin of 70 g/L. Age-related pathophysiological changes provide some explanation as to why older adults have a lower tolerance for anemia than younger adults. This indicates the need for patient blood management hemoglobin thresholds specific to older as distinct from younger adults. The primary application of this model is in the consideration of patients rehabilitating to life outside hospital. It is important to note that pathophysiological changes associated with critical illness and major surgery are more complex than can be described in a simple model based on cardiac output and hemoglobin concentration. However, our review of oxygen transport and delivery in health and disease states allows the model to be considered in the context of treatment decisions for anemic adults in a range of hospital and community settings.

Research paper thumbnail of Cost–utility analysis comparing hospital‐based intravenous immunoglobulin with home‐based subcutaneous immunoglobulin in patients with secondary immunodeficiency

Vox Sanguinis

for their clinical advice, and Brett Darracott and Evana Gaylard for providing the finance inform... more for their clinical advice, and Brett Darracott and Evana Gaylard for providing the finance information for the model.

Research paper thumbnail of Blood management in hip fractures; are we leaving it too late? A retrospective observational study

BMC Geriatrics

Background: Anaemia in hip fracture patients has been associated with increased risk of allogenic... more Background: Anaemia in hip fracture patients has been associated with increased risk of allogenic blood transfusion (ABT), poorer functional outcomes and increased mortality. Few studies have reported the prevalence of anaemia on admission or its progression prior to surgery in this cohort. We aimed to measure the prevalence of anaemia on admission in older persons who sustain a hip fracture, identify if anaemia develops or progresses prior to surgery, and to report associations with outcome. Methods: A retrospective, observational study was undertaken in a regional hospital. All patients aged 60 and over, admitted with a primary hip fracture resulting from a simple fall, in the 12 months of 2014 were included. The World Health Organization (WHO) definition of anaemia was used. Pathology databases and clinical records were reviewed to collect data. Repeated measures ANOVA's were used to quantify the progression of anaemia prior to surgery, and Chi square test were used to report associations with outcome variables. Results: Two hundred sixty-one patients were identified, median age was 81 years. There were twice as many females as males and just over half the sample had extracapsular fractures. Anaemia was present on admission in 45% (n = 117), highest incidence of anaemia occurred in males 52.0% (n = 39), extracapsular fractures 41.9% (n = 78) and those aged over 80 years 49.7% (n = 91). Progression of anaemia prior to surgery was significant in all groups (p < 0.05), with the greatest reduction seen in extracapsular fractures. Pre-surgery reduction in Hb was recorded in 82.3% of patients between admission and day 1, and in 71.4% between admission and day 2. There was significant association between anaemia on admission and PRBC transfusion (p < 0.05), in hospital mortality (p < 0.05) however no association with the use of antiplatelet or anticoagulant medication, nor LOS. Conclusions: The findings demonstrate that pre-surgical anaemia in older hip fracture patients is associated with a PRBC transfusion and increased hospital mortality. Importantly, it also identified that patients continue to bleed after admission, leading to the development of or worsening anaemia. Thus, identification anaemia in the pre-surgical period provides an opportunity for treatment to avoid transfusions and improve patient outcomes.

Research paper thumbnail of A retrospective explanatory case study of the implementation of a bleeding management quality initiative, in an Australian cardiac surgery unit

Australian Critical Care

Background: Bleeding management in cardiac surgery is challenging. Many guidelines exist to suppo... more Background: Bleeding management in cardiac surgery is challenging. Many guidelines exist to support bleeding management; however, literature demonstrates wide variation in practice. In 2012, a quality initiative was undertaken at The Prince Charles Hospital, Australia to improve bleeding management for cardiac surgery patients. The implementation of the quality initiative resulted in significant reductions in the incidence of blood transfusion, re-exploration for bleeding; superficial leg and chest wound infections; length of hospital stay, and cost. Given the success of the initiative, we sought to answer the question; "How and why was the process of implementing a bleeding management quality initiative in the cardiac surgery unit successful, and sustainable?" Methods: A retrospective explanatory case study design was chosen to explore the quality initiative. Analysis of the evidence was reviewed through phases of the 'Knowledgeto Action' planned change model. Data was derived from: (1) document analysis, (2) direct observation of the local environment, (3) clinical narratives from interviews, and analysed with a triangulation approach. The study period extended from 10/2011 to 6/2013. Results: Results demonstrated the complexity of changing practice, as well as the significant amount of dedicated time and effort required to support individual, department and system wide change. Results suggest that while many clinicians were aware of the potential to apply improved practice, numerous barriers and challenges needed to be overcome to implement change across multiple disciplines and departments. Conclusions: The key successful components of the QI were revealed through the case study analysis as: (1) an appropriately skilled project manager to facilitate the implementation process; (2) tools to support changes in workflow and decision making including a bleeding management treatment algorithm with POCCTs; (3) strong clinical leadership from the multidisciplinary team and; (4) the evolution of the project manager position into a perpetual clinical position to support sustainability.

Research paper thumbnail of Questioning the benefit of restrictive transfusion practice in older adults

ISBT Science Series

Restrictive transfusion practice is widely promoted, with many international guidelines recommend... more Restrictive transfusion practice is widely promoted, with many international guidelines recommending haemoglobin thresholds of 70 to 80 g/l for adult patients who are asymptomatic. Randomized controlled trials comparing outcomes associated with liberal and restrictive transfusion strategies underpin this approach. Meta‐analyses including trials of adult patients >18 years of age have concluded that restrictive practice is noninferior to liberal transfusion approaches. A restrictive approach to transfusion reduces resource consumption and cost, as well as the hazards associated with unnecessary exposure to blood products. Although adults aged ≥65 years consume over half of the blood supply, there are few randomized controlled transfusion trials exclusive to this cohort. Our 2017 meta‐analysis of a small number of trials focussed on older adults found that higher transfusion haemoglobin thresholds were associated with lower mortality and fewer cardiac complications in this age group. Other studies have also shown that higher transfusion haemoglobin thresholds are beneficial in older adults. This paper presents recent evidence regarding transfusion outcomes in older adults and discusses aspects of the pathophysiology of ageing that impact on the reduced resilience of older patients to anaemic states. This evidence challenges the use of Hb thresholds that apply across the adult lifespan, regardless of age. It proposes that older age be considered as a risk factor in assessing transfusion requirements, and that transfusion practice in older adults may require higher haemoglobin thresholds than for younger adults.

Research paper thumbnail of Fluid resuscitation with 0.9% saline alters haemostasis in an ovine model of endotoxemic shock

Thrombosis Research

Introduction: Fluid resuscitation is a cornerstone of severe sepsis management, however there are... more Introduction: Fluid resuscitation is a cornerstone of severe sepsis management, however there are many uncertainties surrounding the type and volume of fluid that is administered. The entire spectrum of coagulopathies can be seen in sepsis, from asymptomatic aberrations to fulminant disseminated intravascular coagulation (DIC). The aim of this study was to determine if fluid resuscitation with saline contributes to the haemostatic derangements in an ovine model of endotoxemic shock. Materials and Methods: Twenty-one adult female sheep were randomly divided into no endotoxemia (n=5) or endotoxemia groups (n=16) with an escalating dose of lipopolysaccharide (LPS) up to 4 µg/kg/hr administered to achieve a mean arterial pressure below 60mmHg. Endotoxemia sheep received either no bolus fluid resuscitation (n=8) or a 0.9% saline bolus (40 mL/kg over 60 minutes) (n=8). No endotoxemia, saline only animals (n=5) underwent fluid resuscitation with a 0.9% bolus of saline as detailed above. Hemodynamic support with vasopressors was initiated if needed, to maintain a mean arterial pressure (MAP) of 60-65mmHg in all the groups. Results: Rotational thromboelastometry (ROTEM®) and conventional coagulation biomarker tests demonstrated sepsis induced derangements to secondary haemostasis. This effect was exacerbated by saline fluid resuscitation, with low pH (p = 0.036), delayed clot initiation and formation together with deficiencies in naturally occurring anti-coagulants antithrombin (p = 0.027) and Protein C (p = 0.001).

Research paper thumbnail of Incremental research approach to describing the pharmacokinetics of ciprofloxacin during extracorporeal membrane oxygenation

Critical care and resuscitation : journal of the Australasian Academy of Critical Care Medicine, 2017

Significant interactions between drugs, extracorporeal membrane oxygenation (ECMO) circuits and c... more Significant interactions between drugs, extracorporeal membrane oxygenation (ECMO) circuits and critical illness may affect the pharmacokinetic properties of antibiotics in critically ill patients receiving ECMO. To describe the pharmacokinetic properties of ciprofloxacin during ECMO by integrating pre-clinical findings (ie, ex vivo and in vivo ovine models) to a critically ill patient. An ex vivo model of an ECMO circuit was used to describe ciprofloxacin concentration changes over 24 hours. An in vivo ovine model of ECMO was used to describe the population pharmacokinetic properties of ciprofloxacin in three different groups of sheep, and to investigate sources of pharmacokinetic variability. In the final phase, data from a 39-year-old critically ill man was used to validate the findings from the ovine pharmacokinetic model. In the ex vivo model of ECMO circuits, the median concentrations of ciprofloxacin at baseline and at 24 hours after ciprofloxacin infusion were similar. The t...

Research paper thumbnail of Evidence of ECMO induced changes to haemostasis in an ovine model

Research paper thumbnail of Outcomes of restrictive versus liberal transfusion strategies in older adults from nine randomised controlled trials: a systematic review and meta-analysis

The Lancet Haematology

Guidelines for patient blood management recommend restrictive transfusion practice for most adult... more Guidelines for patient blood management recommend restrictive transfusion practice for most adult patients. These guidelines are supported by evidence from randomised controlled trials (RCTs); however, one of the patient groups not explicitly examined in these studies is the geriatric population. We examined RCTs relevant to transfusion outcomes in older patients. Our aim was to determine whether special guidelines are warranted for geriatric patients, recognising the different pathophysiological characteristics of this group. For this systematic review and meta-analysis, we searched PubMed, Scopus, and the Cochrane Library databases from their inception to May 5, 2017, for evidence relating to transfusion outcomes in adults aged 65 years and older. This criterion was widened to include RCTs where a substantial proportion of the study population was older than 65 years. We also included study populations of all clinical settings, and did not limit the search by date, language, or study type. For articles not in English, only available translations of the abstracts were reviewed. Studies were excluded if they did not specify age. Observational studies and duplicate patient and outcome data from studies that generated multiple publications were also excluded. We screened bibliographies of retrieved articles for additional publications. We analysed data extracted from published RCTs comparing restrictive and liberal transfusion strategies in older adults. We generated fixed effects risk ratios (RR) for pooled study data using the Mantel-Haenszel method. Primary outcomes were 30-day and 90-day mortality events for patients enrolled in restrictive and liberal transfusion study groups. We included intention-to-treat outcome data in the meta-analysis when available, otherwise we used per-protocol outcome data. 686 articles were identified by the search, and a further 37 by the snowball approach. Of these articles, 13 eligible papers described findings from nine RCTs (five trials investigating orthopaedic surgery, three cardiac surgery, and one oncology surgery; including 5780 patients). The risk of 30-day mortality was higher in older patients who followed a restrictive transfusion strategy than in those who followed a liberal transfusion strategy (risk ratio [RR] 1·36, 95% CI 1·05-1·74; p=0·017). The risk of 90-day mortality was also higher in those who followed a restrictive transfusion strategy than in those who followed a liberal transfusion strategy (RR 1·45, 95% CI 1·05-1·98; p=0·022). Liberal transfusion strategies might produce better outcomes in geriatric patients than restrictive transfusion strategies. This outcome contradicts current restrictive transfusion approaches. Population ageing will challenge resources globally, and this finding has implications for blood supply and demand, and optimal care of older adults. Further research is needed to formulate evidence-based transfusion practice across clinical specialties specific to the geriatric population, and to examine resource effects. Australia&#39;s National Blood Authority.

Research paper thumbnail of Evidence of altered haemostasis in an ovine model of venovenous extracorporeal membrane oxygenation support

Critical care (London, England), Jul 29, 2017

Extracorporeal membrane oxygenation (ECMO) is a life-saving modality used in the management of ca... more Extracorporeal membrane oxygenation (ECMO) is a life-saving modality used in the management of cardiopulmonary failure that is refractory to conventional medical and surgical therapies. The major problems clinicians face are bleeding and clotting, which can occur simultaneously. To discern the impact of pulmonary injury and ECMO on the host's haemostatic response, we developed an ovine model of smoke-induced acute lung injury (S-ALI) and ECMO. The aims of this study were to determine if the ECMO circuit itself altered haemostasis and if this was augmented in a host with pulmonary injury. Twenty-seven South African meat merino/Border Leicester Cross ewes underwent instrumentation. Animals received either sham injury (n = 12) or S-ALI (n = 15). Control animal groups consisted of healthy controls (ventilation only for 24 h) (n = 4), ECMO controls (ECMO only for 24 h) (n = 8) and S-ALI controls (S-ALI but no ECMO for 24 h) (n = 7). The test group comprised S-ALI sheep placed on ECMO...

Research paper thumbnail of Inflammation and lung injury in an ovine model of extracorporeal membrane oxygenation support

American journal of physiology. Lung cellular and molecular physiology, 2016

Extracorporeal membrane oxygenation (ECMO) is a life-saving treatment for patients with severe re... more Extracorporeal membrane oxygenation (ECMO) is a life-saving treatment for patients with severe refractory cardiorespiratory failure. Exposure to the ECMO circuit is thought to trigger/exacerbate inflammation. Determining whether inflammation is the result of the patients' underlying pathologies or the ECMO circuit is difficult. To discern how different insults contribute to the inflammatory response, we developed an ovine model of lung injury and ECMO to investigate the impact of smoke-induced lung injury and ECMO in isolation and cumulatively on pulmonary and circulating inflammatory cells, cytokines, and tissue remodeling. Sheep receiving either smoke-induced acute lung injury (S-ALI) or sham injury were placed on veno-venous (VV) ECMO lasting either 2 or 24 h, with controls receiving conventional ventilation only. Lung tissue, bronchoalveolar fluid, and plasma were analyzed by RT-PCR, immunohistochemical staining, and zymography to assess inflammatory cells, cytokines, and ma...

Research paper thumbnail of The Sheep as a Transfusion Model: Comparison of the Storage Lesion of Human and Ovine Red Blood Cell Units

Transfusion Medicine, 2013

Introduction: There is growing awareness of risks related to transfusion of stored blood products... more Introduction: There is growing awareness of risks related to transfusion of stored blood products. Animal models (e.g. ovine) will bevital to investigating the underlying mechanisms. This study aimed to characterise specific aspects of the storage lesion of ovine (ov) packed red blood cell (PRBC) units and compare these to equivalent human PRBC (huPRBC) units, expanding upon our previous reports of biochemical changes and haemolysis rates. Methods: Whole blood was collected from adult Merino ewes (n=5) into blood packs containing citrate-phosphate-dextrose (CPD) and processed into leucodepleted ovPRBCs preserved in saline, adenine, glucose and mannitol (SAGM) additive solution. Equivalent huPRBCs (n=5) were provided by the Australian Red Cross Blood Service. OvPRBCs and huPRBCs were stored at 2-6 ◦ C for 42 days, and samples were collected aseptically at weekly intervals (days 1, 7, 14, 21, 28, 35 and 42). Samples underwent testing for 2,3-diphosphoglycerate (2,3- DPG) and adenosine...

Research paper thumbnail of Sheep red blood cells for transfusion: is the storage lesion comparable to human red blood cells?

Research paper thumbnail of Primary immunodeficiency disease: a cost-utility analysis comparing intravenous vs subcutaneous immunoglobulin replacement therapy in Australia

BACKGROUND Hospital-based intravenous immunoglobulin (IVIg) treatment has been the standard treat... more BACKGROUND Hospital-based intravenous immunoglobulin (IVIg) treatment has been the standard treatment mode for patients with primary immunodeficiency disease (PID). With the newer home-based subcutaneous immunoglobulin (SCIg) becoming approved for use in most countries, the question arises as to whether SCIg is a cost-effective treatment mode compared to IVIg in Australia. MATERIALS AND METHODS We developed a Markov cohort simulation model with six health states: PID without infection, PID with infection treated at home or hospital, bronchiectasis without infection, bronchiectasis with infection treated at home or hospital, bronchiectasis with chronic Pseudomonas aeruginosa infection, and death, from an Australian healthcare system perspective. A 10-year time horizon with weekly cycles was chosen, and the expected costs and quality-adjusted life-years (QALYs) of the two treatment options estimated. RESULTS The cumulative 10-year cost per patient was 297,547 Australian dollars (A$) w...

Research paper thumbnail of Unplanned blood use within 24 hours of emergency department presentation: A cohort study in an ageing population

Emergency Medicine Australasia

OBJECTIVE This research aims to elucidate drivers of blood use in an older population, with a foc... more OBJECTIVE This research aims to elucidate drivers of blood use in an older population, with a focus on unplanned transfusions following ED presentation. METHODS In a retrospective cohort study we examined 2015 data for ED presentations and blood use in two hospitals serving a population containing a high proportion (21%) of adults aged ≥65 years. Unplanned blood use was defined as any transfusion ≤24 h of presentation. Data were analysed by age, sex, Major Diagnostic Category, triage category and time to transfusion. RESULTS A total of 5294 blood components were transfused, comprising red cells (n = 3784), fresh frozen plasma (n = 657), platelets (n = 563) and cryoprecipitate (n = 290). Men aged ≥65 years were the highest users (40%, 2107 components). Unplanned transfusions accounted for 28% (n = 1057) of annual red cell use. Of 85 014 ED presentations, 494 (0.6%) were associated with unplanned red cell transfusion. Four Major Diagnostic Categories accounted for 81% (n = 853) of unplanned red cell use: gastrointestinal (n = 375), haematology (n = 267), trauma (n = 144) and cardiovascular (n = 67). Over one-fifth of unplanned transfusions (21%, n = 222 of 1057) were associated with ICD-10 codes for anaemia as a reason for presentation within the Haematology Major Diagnostic Category. Adults aged ≥65 years accounted for 62% of overall red cell use and 61% of transfusions ≤24 h of presentation. Odds of unplanned red cell transfusion increased with age, peaking at odds ratio 28.5 (95% confidence interval 14.2-57.4) in those aged 85 years and above. CONCLUSIONS Unplanned blood use accounted for 28% of annual hospital blood consumption. Blood component use increased with age and was greatest in older men. A significant burden of anaemia treatment was identified by the ED.

Research paper thumbnail of Research Article – BMC Health Service Research (IF -1.93) Barriers and Facilitators to Implementing Evidence Based Bleeding Management in Australian Cardiac Surgery Units: A Qualitative Interview Study Analysed With the Theoretical Domains Framework and COM-B Model

BackgroundBleeding during cardiac surgery is a common complication that often requires the transf... more BackgroundBleeding during cardiac surgery is a common complication that often requires the transfusion of blood products. The combination of bleeding and blood product transfusion incrementally increases adverse outcomes including infection and mortality. Following bleeding management guideline recommendationscould assist with minimising risk but adherence is not high, and the cause for lack of adherence is not well understood. This study aimed to identify barriers and facilitators to practicing and implementing evidenced-based bleeding management in Australian cardiac surgery units. MethodsWe used a qualitative descriptive design to conduct semi-structuredinterviews with Australian cardiac surgeons, anaesthetists and perfusionists.The Theoretical Domains Framework (TDF) was utilised toguide interviews and thematically analyse the data. Categorised data were then linkedwith the three key domains of the COM-B model (capability, opportunity, and motivation) to explore and understand b...

Research paper thumbnail of Barriers and Facilitators to Implementing Evidence Based Bleeding Management in Australian Cardiac Surgery Units: A Qualitative Interview study analysed with the Theoretical Domains Framework and COM-B model

BackgroundBleeding during cardiac surgery is a common complication that often requires the transf... more BackgroundBleeding during cardiac surgery is a common complication that often requires the transfusion of blood products. The combination of bleeding and blood product transfusion incrementally increases adverse outcomes including infection and mortality. Following bleeding management guideline recommendations could assist with minimising risk but adherence is not high, and the cause for lack of adherence is not well understood. This study aimed to identify barriers and facilitators to practicing and implementing evidenced-based intra-operative, bleeding management in Australian cardiac surgery units. MethodsWe used a qualitative descriptive design to conduct semi-structured interviews with Australian cardiac surgeons, anaesthetists and perfusionists. The Theoretical Domains Framework (TDF) was utilised to guide interviews and thematically analyse the data. Categorised data were then linked with the three key domains of the COM-B model (capability, opportunity, and motivation) to ex...

Research paper thumbnail of Bleeding Management Practices of Australian Cardiac Surgeons, Anesthesiologists and Perfusionists: A Cross-Sectional National Survey Incorporating the Theoretical Domains Framework (TDF) and COM-B Model

Journal of Multidisciplinary Healthcare

Purpose: Excessive bleeding is an acknowledged consequence of cardiac surgery, occurring in up to... more Purpose: Excessive bleeding is an acknowledged consequence of cardiac surgery, occurring in up to 10% of adult patients. This clinically important complication leads to poorer patient outcomes. Clinical practice guidelines are available to support best practice however variability in bleeding management practice and related adverse outcomes still exist. This study had two objectives: 1) to gain insight into current bleeding management practice for adult cardiac surgery in Australia and how that compared to guidelines and literature; and 2) to understand perceived difficulties clinicians face implementing improvements in bleeding management. Methods: A national cross-sectional questionnaire survey was utilized. Perspectives were sought from cardiac surgeons, cardiac anesthesiologists and perfusionists. Thirty-nine closedended questions focused on routine bleeding management practices to address pre and intraoperative care. One open-ended question was asked; "What would assist you to improve bleeding management with cardiac surgery patients?" Quantitative data were analysed with SPSS. Qualitative data were categorized into the domains of the Theoretical Domains Framework; the domains were then mapped to the COMB model. Results: Survey responses from 159 Anesthesiologists, 39 cardiac surgeons and 86 perfusionists were included (response rate 37%). Four of the recommendations queried in this survey were reported as routinely adhered to < 50% of the time, 9 queried recommendations were adhered to 51-75% of the time and 4 recommendations were routinely followed >76% of the time. Conclusion: There is a wide variation in peri-operative bleeding management practice among cardiac anaesthesiologists, surgeons and perfusionists in Australian cardiac surgery units. Conceptualizing factors believed necessary to improve practice with the TDF and COMB model found that bleeding management could be improved with a standardized approach including; point of care diagnostic assays, a bleeding management algorithm, access to concentrated coagulation factors, cardiac surgery specific bleeding management education, multidisciplinary team agreement and support, and an overarching national approach.

Research paper thumbnail of Dissimilar Respiratory and Hemodynamic Responses In TRALI Induced by Stored Red Cells and Whole Blood Platelets

Blood

1112 Background & Aims: Transfusion-related acute lung injury (TRALI) is a predominant cause of t... more 1112 Background & Aims: Transfusion-related acute lung injury (TRALI) is a predominant cause of transfusion-related morbidity and mortality, however the mechanism underlying its development remains undefined. We have previously demonstrated that heat-treated supernatant from stored (day 5) human whole blood platelet components (d5-PLT-S/N) cause TRALI in lipopolysaccharide (LPS) treated sheep (Tung et al. Vox Sang 2010). This two-event in-vivo model was used to further investigate TRALI due to heat-treated supernatant from stored (day 42) human red cells (d42-PRBC-S/N), and a comparison of the two models is reported here. Methods: Sheep were infused with LPS (15μg/kg; to model a first event of clinical infection), and then transfused with either d5-WB-PLT-S/N or d42-PRBC-S/N (10% of estimated blood volume; second event), with saline and supernatant from fresh blood components as controls. Microarray techniques were used to analyze cytokine and chemokine expression levels in both the...

Research paper thumbnail of Recipient T and B Lymphocytes Dictate the Severity of Antibody-Mediated Transfusion-Related Acute Lung Injury (TRALI)

Blood

641 Transfusion-related acute lung injury (TRALI) is a serious complication of transfusion and ha... more 641 Transfusion-related acute lung injury (TRALI) is a serious complication of transfusion and has been ranked as the leading cause of transfusion-related fatalities. The majority (approx. 80%) of TRALI reactions are associated with and probably initiated by donor alloantibodies recognizing recipient granulocytes and/or human leukocytes antigens (HLA). Nonetheless, many details of the immunopathogenesis of TRALI are unknown. Previous studies have shown that a murine anti-MHC (H-2Kd) class I antibody (clone 34-1-2s) can induce TRALI in mice (Looney et al J Clin Invest. 116:1615,2006) and we utilized this model in an attempt to understand the role that recipient lymphocytes might play in TRALI reactions. BALB/c (H-2d) mice were injected iv with titrations of 34-1-2s and body temperature, morbidity/mortality, pulmonary granulocyte accumulation and serum levels of MIP-2 (the murine analog of human neutrophil chemokine IL8) were measured at various time points. Results showed that when B...

Research paper thumbnail of Impacts of Aging on Anemia Tolerance, Transfusion Thresholds, and Patient Blood Management

Transfusion Medicine Reviews

Evidence-based patient blood management guidelines commonly recommend restrictive hemoglobin thre... more Evidence-based patient blood management guidelines commonly recommend restrictive hemoglobin thresholds of 70 to 80 g/L for asymptomatic adults. However, most transfusion trials have enrolled adults across a broad age span, with few exclusive to older adults. Our recent meta-analysis of transfusion trials that focused on older adults paradoxically found lower mortality and fewer cardiac complications when these patients were managed using higher hemoglobin thresholds. We postulate that declining cardiac output with age contributes to deteriorating oxygen delivery capacity which impacts anemia-associated outcomes in older adults and propose a model to explain this age-related difference. We reviewed evidence concerning the pathophysiology of aging to explore the disparity in transfusion trial outcomes related to hemoglobin thresholds in different age groups. The literature was searched for normative cardiac output values at different ages in healthy adults. Using normative peak cardiac output data, we modeled oxygen delivery capacity in young, middle-aged, and older adults at a range of hemoglobin levels. Cardiovascular and pulmonary systems are impacted by age-related pathophysiological changes. Diminishing peak cardiac output associated with aging reduces the maximal oxygen delivery achievable under metabolic stress. Hence, at low hemoglobin levels, older adults are more susceptible to tissue hypoxia than younger adults. Our model predicts that an older adult with a hemoglobin of 100 g/L has a similar peak oxygen delivery capacity to a young adult with a hemoglobin of 70 g/L. Age-related pathophysiological changes provide some explanation as to why older adults have a lower tolerance for anemia than younger adults. This indicates the need for patient blood management hemoglobin thresholds specific to older as distinct from younger adults. The primary application of this model is in the consideration of patients rehabilitating to life outside hospital. It is important to note that pathophysiological changes associated with critical illness and major surgery are more complex than can be described in a simple model based on cardiac output and hemoglobin concentration. However, our review of oxygen transport and delivery in health and disease states allows the model to be considered in the context of treatment decisions for anemic adults in a range of hospital and community settings.

Research paper thumbnail of Cost–utility analysis comparing hospital‐based intravenous immunoglobulin with home‐based subcutaneous immunoglobulin in patients with secondary immunodeficiency

Vox Sanguinis

for their clinical advice, and Brett Darracott and Evana Gaylard for providing the finance inform... more for their clinical advice, and Brett Darracott and Evana Gaylard for providing the finance information for the model.

Research paper thumbnail of Blood management in hip fractures; are we leaving it too late? A retrospective observational study

BMC Geriatrics

Background: Anaemia in hip fracture patients has been associated with increased risk of allogenic... more Background: Anaemia in hip fracture patients has been associated with increased risk of allogenic blood transfusion (ABT), poorer functional outcomes and increased mortality. Few studies have reported the prevalence of anaemia on admission or its progression prior to surgery in this cohort. We aimed to measure the prevalence of anaemia on admission in older persons who sustain a hip fracture, identify if anaemia develops or progresses prior to surgery, and to report associations with outcome. Methods: A retrospective, observational study was undertaken in a regional hospital. All patients aged 60 and over, admitted with a primary hip fracture resulting from a simple fall, in the 12 months of 2014 were included. The World Health Organization (WHO) definition of anaemia was used. Pathology databases and clinical records were reviewed to collect data. Repeated measures ANOVA's were used to quantify the progression of anaemia prior to surgery, and Chi square test were used to report associations with outcome variables. Results: Two hundred sixty-one patients were identified, median age was 81 years. There were twice as many females as males and just over half the sample had extracapsular fractures. Anaemia was present on admission in 45% (n = 117), highest incidence of anaemia occurred in males 52.0% (n = 39), extracapsular fractures 41.9% (n = 78) and those aged over 80 years 49.7% (n = 91). Progression of anaemia prior to surgery was significant in all groups (p < 0.05), with the greatest reduction seen in extracapsular fractures. Pre-surgery reduction in Hb was recorded in 82.3% of patients between admission and day 1, and in 71.4% between admission and day 2. There was significant association between anaemia on admission and PRBC transfusion (p < 0.05), in hospital mortality (p < 0.05) however no association with the use of antiplatelet or anticoagulant medication, nor LOS. Conclusions: The findings demonstrate that pre-surgical anaemia in older hip fracture patients is associated with a PRBC transfusion and increased hospital mortality. Importantly, it also identified that patients continue to bleed after admission, leading to the development of or worsening anaemia. Thus, identification anaemia in the pre-surgical period provides an opportunity for treatment to avoid transfusions and improve patient outcomes.

Research paper thumbnail of A retrospective explanatory case study of the implementation of a bleeding management quality initiative, in an Australian cardiac surgery unit

Australian Critical Care

Background: Bleeding management in cardiac surgery is challenging. Many guidelines exist to suppo... more Background: Bleeding management in cardiac surgery is challenging. Many guidelines exist to support bleeding management; however, literature demonstrates wide variation in practice. In 2012, a quality initiative was undertaken at The Prince Charles Hospital, Australia to improve bleeding management for cardiac surgery patients. The implementation of the quality initiative resulted in significant reductions in the incidence of blood transfusion, re-exploration for bleeding; superficial leg and chest wound infections; length of hospital stay, and cost. Given the success of the initiative, we sought to answer the question; "How and why was the process of implementing a bleeding management quality initiative in the cardiac surgery unit successful, and sustainable?" Methods: A retrospective explanatory case study design was chosen to explore the quality initiative. Analysis of the evidence was reviewed through phases of the 'Knowledgeto Action' planned change model. Data was derived from: (1) document analysis, (2) direct observation of the local environment, (3) clinical narratives from interviews, and analysed with a triangulation approach. The study period extended from 10/2011 to 6/2013. Results: Results demonstrated the complexity of changing practice, as well as the significant amount of dedicated time and effort required to support individual, department and system wide change. Results suggest that while many clinicians were aware of the potential to apply improved practice, numerous barriers and challenges needed to be overcome to implement change across multiple disciplines and departments. Conclusions: The key successful components of the QI were revealed through the case study analysis as: (1) an appropriately skilled project manager to facilitate the implementation process; (2) tools to support changes in workflow and decision making including a bleeding management treatment algorithm with POCCTs; (3) strong clinical leadership from the multidisciplinary team and; (4) the evolution of the project manager position into a perpetual clinical position to support sustainability.

Research paper thumbnail of Questioning the benefit of restrictive transfusion practice in older adults

ISBT Science Series

Restrictive transfusion practice is widely promoted, with many international guidelines recommend... more Restrictive transfusion practice is widely promoted, with many international guidelines recommending haemoglobin thresholds of 70 to 80 g/l for adult patients who are asymptomatic. Randomized controlled trials comparing outcomes associated with liberal and restrictive transfusion strategies underpin this approach. Meta‐analyses including trials of adult patients >18 years of age have concluded that restrictive practice is noninferior to liberal transfusion approaches. A restrictive approach to transfusion reduces resource consumption and cost, as well as the hazards associated with unnecessary exposure to blood products. Although adults aged ≥65 years consume over half of the blood supply, there are few randomized controlled transfusion trials exclusive to this cohort. Our 2017 meta‐analysis of a small number of trials focussed on older adults found that higher transfusion haemoglobin thresholds were associated with lower mortality and fewer cardiac complications in this age group. Other studies have also shown that higher transfusion haemoglobin thresholds are beneficial in older adults. This paper presents recent evidence regarding transfusion outcomes in older adults and discusses aspects of the pathophysiology of ageing that impact on the reduced resilience of older patients to anaemic states. This evidence challenges the use of Hb thresholds that apply across the adult lifespan, regardless of age. It proposes that older age be considered as a risk factor in assessing transfusion requirements, and that transfusion practice in older adults may require higher haemoglobin thresholds than for younger adults.

Research paper thumbnail of Fluid resuscitation with 0.9% saline alters haemostasis in an ovine model of endotoxemic shock

Thrombosis Research

Introduction: Fluid resuscitation is a cornerstone of severe sepsis management, however there are... more Introduction: Fluid resuscitation is a cornerstone of severe sepsis management, however there are many uncertainties surrounding the type and volume of fluid that is administered. The entire spectrum of coagulopathies can be seen in sepsis, from asymptomatic aberrations to fulminant disseminated intravascular coagulation (DIC). The aim of this study was to determine if fluid resuscitation with saline contributes to the haemostatic derangements in an ovine model of endotoxemic shock. Materials and Methods: Twenty-one adult female sheep were randomly divided into no endotoxemia (n=5) or endotoxemia groups (n=16) with an escalating dose of lipopolysaccharide (LPS) up to 4 µg/kg/hr administered to achieve a mean arterial pressure below 60mmHg. Endotoxemia sheep received either no bolus fluid resuscitation (n=8) or a 0.9% saline bolus (40 mL/kg over 60 minutes) (n=8). No endotoxemia, saline only animals (n=5) underwent fluid resuscitation with a 0.9% bolus of saline as detailed above. Hemodynamic support with vasopressors was initiated if needed, to maintain a mean arterial pressure (MAP) of 60-65mmHg in all the groups. Results: Rotational thromboelastometry (ROTEM®) and conventional coagulation biomarker tests demonstrated sepsis induced derangements to secondary haemostasis. This effect was exacerbated by saline fluid resuscitation, with low pH (p = 0.036), delayed clot initiation and formation together with deficiencies in naturally occurring anti-coagulants antithrombin (p = 0.027) and Protein C (p = 0.001).

Research paper thumbnail of Incremental research approach to describing the pharmacokinetics of ciprofloxacin during extracorporeal membrane oxygenation

Critical care and resuscitation : journal of the Australasian Academy of Critical Care Medicine, 2017

Significant interactions between drugs, extracorporeal membrane oxygenation (ECMO) circuits and c... more Significant interactions between drugs, extracorporeal membrane oxygenation (ECMO) circuits and critical illness may affect the pharmacokinetic properties of antibiotics in critically ill patients receiving ECMO. To describe the pharmacokinetic properties of ciprofloxacin during ECMO by integrating pre-clinical findings (ie, ex vivo and in vivo ovine models) to a critically ill patient. An ex vivo model of an ECMO circuit was used to describe ciprofloxacin concentration changes over 24 hours. An in vivo ovine model of ECMO was used to describe the population pharmacokinetic properties of ciprofloxacin in three different groups of sheep, and to investigate sources of pharmacokinetic variability. In the final phase, data from a 39-year-old critically ill man was used to validate the findings from the ovine pharmacokinetic model. In the ex vivo model of ECMO circuits, the median concentrations of ciprofloxacin at baseline and at 24 hours after ciprofloxacin infusion were similar. The t...

Research paper thumbnail of Evidence of ECMO induced changes to haemostasis in an ovine model

Research paper thumbnail of Outcomes of restrictive versus liberal transfusion strategies in older adults from nine randomised controlled trials: a systematic review and meta-analysis

The Lancet Haematology

Guidelines for patient blood management recommend restrictive transfusion practice for most adult... more Guidelines for patient blood management recommend restrictive transfusion practice for most adult patients. These guidelines are supported by evidence from randomised controlled trials (RCTs); however, one of the patient groups not explicitly examined in these studies is the geriatric population. We examined RCTs relevant to transfusion outcomes in older patients. Our aim was to determine whether special guidelines are warranted for geriatric patients, recognising the different pathophysiological characteristics of this group. For this systematic review and meta-analysis, we searched PubMed, Scopus, and the Cochrane Library databases from their inception to May 5, 2017, for evidence relating to transfusion outcomes in adults aged 65 years and older. This criterion was widened to include RCTs where a substantial proportion of the study population was older than 65 years. We also included study populations of all clinical settings, and did not limit the search by date, language, or study type. For articles not in English, only available translations of the abstracts were reviewed. Studies were excluded if they did not specify age. Observational studies and duplicate patient and outcome data from studies that generated multiple publications were also excluded. We screened bibliographies of retrieved articles for additional publications. We analysed data extracted from published RCTs comparing restrictive and liberal transfusion strategies in older adults. We generated fixed effects risk ratios (RR) for pooled study data using the Mantel-Haenszel method. Primary outcomes were 30-day and 90-day mortality events for patients enrolled in restrictive and liberal transfusion study groups. We included intention-to-treat outcome data in the meta-analysis when available, otherwise we used per-protocol outcome data. 686 articles were identified by the search, and a further 37 by the snowball approach. Of these articles, 13 eligible papers described findings from nine RCTs (five trials investigating orthopaedic surgery, three cardiac surgery, and one oncology surgery; including 5780 patients). The risk of 30-day mortality was higher in older patients who followed a restrictive transfusion strategy than in those who followed a liberal transfusion strategy (risk ratio [RR] 1·36, 95% CI 1·05-1·74; p=0·017). The risk of 90-day mortality was also higher in those who followed a restrictive transfusion strategy than in those who followed a liberal transfusion strategy (RR 1·45, 95% CI 1·05-1·98; p=0·022). Liberal transfusion strategies might produce better outcomes in geriatric patients than restrictive transfusion strategies. This outcome contradicts current restrictive transfusion approaches. Population ageing will challenge resources globally, and this finding has implications for blood supply and demand, and optimal care of older adults. Further research is needed to formulate evidence-based transfusion practice across clinical specialties specific to the geriatric population, and to examine resource effects. Australia&#39;s National Blood Authority.

Research paper thumbnail of Evidence of altered haemostasis in an ovine model of venovenous extracorporeal membrane oxygenation support

Critical care (London, England), Jul 29, 2017

Extracorporeal membrane oxygenation (ECMO) is a life-saving modality used in the management of ca... more Extracorporeal membrane oxygenation (ECMO) is a life-saving modality used in the management of cardiopulmonary failure that is refractory to conventional medical and surgical therapies. The major problems clinicians face are bleeding and clotting, which can occur simultaneously. To discern the impact of pulmonary injury and ECMO on the host's haemostatic response, we developed an ovine model of smoke-induced acute lung injury (S-ALI) and ECMO. The aims of this study were to determine if the ECMO circuit itself altered haemostasis and if this was augmented in a host with pulmonary injury. Twenty-seven South African meat merino/Border Leicester Cross ewes underwent instrumentation. Animals received either sham injury (n = 12) or S-ALI (n = 15). Control animal groups consisted of healthy controls (ventilation only for 24 h) (n = 4), ECMO controls (ECMO only for 24 h) (n = 8) and S-ALI controls (S-ALI but no ECMO for 24 h) (n = 7). The test group comprised S-ALI sheep placed on ECMO...

Research paper thumbnail of Inflammation and lung injury in an ovine model of extracorporeal membrane oxygenation support

American journal of physiology. Lung cellular and molecular physiology, 2016

Extracorporeal membrane oxygenation (ECMO) is a life-saving treatment for patients with severe re... more Extracorporeal membrane oxygenation (ECMO) is a life-saving treatment for patients with severe refractory cardiorespiratory failure. Exposure to the ECMO circuit is thought to trigger/exacerbate inflammation. Determining whether inflammation is the result of the patients' underlying pathologies or the ECMO circuit is difficult. To discern how different insults contribute to the inflammatory response, we developed an ovine model of lung injury and ECMO to investigate the impact of smoke-induced lung injury and ECMO in isolation and cumulatively on pulmonary and circulating inflammatory cells, cytokines, and tissue remodeling. Sheep receiving either smoke-induced acute lung injury (S-ALI) or sham injury were placed on veno-venous (VV) ECMO lasting either 2 or 24 h, with controls receiving conventional ventilation only. Lung tissue, bronchoalveolar fluid, and plasma were analyzed by RT-PCR, immunohistochemical staining, and zymography to assess inflammatory cells, cytokines, and ma...