The meaning of acute kidney injury and its relevance to intensive care and anaesthesia.

Acute kidney injury (AKI) is the new consensus term for acute renal failure. The term describes a continuum of kidney injury, a common condition in the critically ill and after major surgery, which is associated with increased mortality. The incidence of AKI in intensive care unit patients in Australia is >30% and sepsis is a major contributory factor. However, there is limited knowledge about its incidence after major surgery, except for cardiac surgery. The creation of staged AKI classification systems (RIFLE [Risk, Injury, Failure, Loss, End-stage], Acute Kidney Injury Network and the new Kidney Disease: Improving Global Outcomes criteria) has accelerated progress in critical care nephrology research by showing that even small changes in serum creatinine are associated with increased risk of death and that this risk increases progressively with severity of AKI. Recent thought and research has cast doubt over previously accepted pathophysiological views of AKI. Moreover, terms such as 'prerenal azotaemia' and 'acute tubular necrosis' are now being challenged as lacking validity, having little supportive evidence and carrying limited clinical utility. In this review, we explore the limitations of animal and human models of AKI and the implications of recent research on our current understanding of the pathophysiology of AKI. In addition, we describe conventional and novel diagnostic methods and therapies, and explore the clinical implications of the effect of fluid administration and perioperative management. Finally, we identify priorities for clinical investigations and future directions in AKI research.

Erythropoietin as a novel brain and kidney protective agent.

Erythropoietin is a 30.4 kDa glycoprotein produced by the kidney, which is mostly known for its physiological function in regulating red blood cell production in the bone marrow Accumulating evidence, however suggests that erythropoietin has additional organ protective effects, which may specifically be useful in protecting the brain and kidneys from injury. Experimental evidence suggests that these protective mechanisms are multi-factorial in nature and may include inhibition of apoptotic cell death, stimulation of cellular regeneration, inhibition of deleterious pathways and promotion of recovery. In this article we review the physiology of erythropoietin, assess previous work that supports the role of erythropoietin as a general tissue protective agent and explain the mechanisms by which it may achieve this tissue protective effect. We then focus on specific laboratory and clinical data that suggest that erythropoietin has a strong brain protective and kidney protective effect. In addition, we comment on the implications of these studies for clinicians at the bedside and for researchers designing controlled trials to further elucidate the true clinical utility of erythropoietin as a neuroprotective and nephroprotective agent. Finally, we describe EPO-TBI, a double-blinded multi-centre randomised controlled trial involving the authors that is being conducted to investigate the organ protective effects of erythropoietin on the brain, and also assesses its effect on the kidneys.

Measuring functional and quality of life outcomes following major head injury: common scales and checklists.

Traumatic brain injury (TBI) is a major public health issue, which results in significant mortality and long term disability. The profound impact of TBI is not only felt by the individuals who suffer the injury but also their care-givers and society as a whole. Clinicians and researchers require reliable and valid measures of long term outcome not only to truly quantify the burden of TBI and the scale of functional impairment in survivors, but also to allow early appropriate allocation of rehabilitation supports. In addition, clinical trials which aim to improve outcomes in this devastating condition require high quality measures to accurately assess the impact of the interventions being studied. In this article, we review the properties of an ideal measure of outcome in the TBI population. Then, we describe the key components and performance of the measurement tools most commonly used to quantify outcome in clinical studies in TBI. These measurement tools include: the Glasgow Outcome Scale (GOS) and extended Glasgow Outcome Scale (GOSe); Disability Rating Scale (DRS); Functional Independence Measure (FIM); Functional Assessment Measure (FAM); Functional Status Examination (FSE) and the TBI-specific and generic quality of life measures used in TBI patients (SF-36 and SF-12, WHOQOL-BREF, SIP, EQ-5D, EBIQ, and QOLIBRI).

Challenging issues in randomised controlled trials.

WHAT THIS TOPIC IS ABOUT: Randomised controlled trials (RCTs) are the most rigorous way of determining whether a cause-effect relation exists between treatment and outcome and are an integral component in the hierarchy of evidence which guide current clinical practice. Whether ensuring the success of a RCT or interpreting the medical literature, it is important to understand the key components of RCT design to assess their quality and therefore the weight which should be attributed to its findings. This article will highlight some of these key components by using a number of ongoing trauma studies being co-ordinated by the Australian and New Zealand Intensive Care Research Centre, Monash University. COMMON PROBLEMS AND CHALLENGES: The quality of many RCTs could be improved by avoiding some common pitfalls, such as (i) unclear hypotheses and multiple objectives, (ii) poor selection of endpoints, (iii) inappropriate subject selection criteria, (iv) non-clinically relevant or feasible treatment/intervention regimens, (v) inadequate randomisation, stratification, blinding, (vi) lack of stratification in small RCTs (vii) inadequate blinding of trials, (viii) insufficient sample size/power, (ix) failure to use intention to treat analysis and (x) failure to anticipate common practical problems encountered during the conduct of a RCT. TIPS FOR RESEARCHERS: The RCTs most likely to be funded and/or be of high quality always address these issues.