Emergency medicine

To the Editor: My observations over the past 10 years as an ambulance paramedic are consistent with the growth in demand for emergency and non-emergency ambulance services in Melbourne.1 Strong demand has been forecast to continue because 60% of patients who are eligible for emergency transport do not currently use ambulance services.2 The increasing demand for ambulance services — an essential component of the Australian health care network — necessitates the development of valid, reliable indicators of quality and safety in prehospital health care, to maintain and improve the quality of that care. As part of the Australian Commission on Safety and Quality in Health Care’s National Indicators Project, the Australian Institute of Health and Welfare (AIHW) has proposed 55 indicators of quality and safety in health care that represent a whole-of-system approach.3 However, this cannot be achieved without the inclusion of ambulance indicators. The AIHW indicators focus mainly on facility-based services (eg, hospitals) and underestimate the interdependence of the health care network. Ambulance services routinely collect information from the wider health care community, representing transported and non-transported patients, including clinical intervention and outcome parameters. These data can be used to identify interventions and outcomes attributable to prehospital health care practice. Improvements in patient sequence management,4 based on Ambulance Victoria research and data from specialised trauma and cardiac arrest registries,5 suggest that ambulance interventions can result in tangible benefits. Ambulance-specific process and outcome indicators would enable more precise attribution of outcomes to prehospital care and assist in apportioning health outcomes across the wider health network. This would directly benefit hospitals because pressure for increased public accountability currently ascribes performance based on risk factors that hospitals cannot influence. Enhanced prehospital indicators could supplement and expand the range of risk parameters that hospitals currently use to adjust hospital performance indicators; this would help mitigate the limitations inherent in comparative public reporting.6 Longer-term benefits include the implementation of alternative models of evidence-based practice, encompassing “treat-and-leave protocols”, and identification of non-hospital referral avenues. Safety is a crucial aspect of alternative practices, and protocols must be formulated and monitored in the light of valid and reliable indicators. Inclusion of ambulance indicators in the National Indicators Project would place ambulance services in a key position to ensure that timely access to safe, high-quality health care is maintained and improved.

Paul A De Vincentis

To the Editor: Since 2008, the Australian Capital Territory’s public acute health care system has successfully been using multiple-parameter and single-parameter track, trigger and response (TTR) systems in parallel for the recognition of and response to clinical deterioration in patients. Jenkins and colleagues correctly identify that there is a general lack of agreement on the use of TTR systems around Australia, although they note that the most commonly used rapid response system is the medical emergency team (MET) alert which is triggered by a single parameter, a vital sign derangement, or a concern for the patient.1 As Jenkins et al suggest, a multiple-parameter TTR system may trigger a response earlier than might occur with MET parameters. In 2007 at Canberra Hospital, a multifaceted before-and-after intervention study of the recognition of and response to patients’ deteriorating conditions found improvements in both patient outcomes and measures of processes of care for patients whose condition was deteriorating.2 The intervention included the installation of a multiple-parameter TTR system, using a modified early warning score3 generated from the degree of derangement of all vital signs and end organ function. Individual vital sign early warning scores were then colour-coded and embedded within newly formatted, human-factors-designed observation charts. Further, before the new system commenced, about 90% of all health care workers (210/234) participated in an education program.4 This program comprised both an e-learning package and a 3-hour, face-to-face, low-fidelity simulation package. It aimed to promote the understanding of the physiological principles of vital signs, and reasons for their measurement and their derangement; it also provided a structure for succinct communication and initial resuscitation. The multiple-parameter TTR system has now been successfully rolled out to all areas of the hospital, including the emergency medical unit, emergency department and medical assessment and planning unit, alongside our MET system. The multiple-parameter TTR system has been a useful tool to engage parent medical teams in reviewing patients at risk of critical illness, and has empowered nurses to call for a MET review, given that the modified early warning score provides further evidence that the patient’s condition is deteriorating. With the use of the systems in parallel and the mandatory training package, MET use has doubled and delays in calling for a MET review have decreased. We would welcome further investigation of the multiple-parameter TTR system that we have adopted, particularly in a multicentre setting.

Imogen A Mitchell · Mary-Ann Kulh · Heather McKay

Objective: To determine the current level of knowledge of first aid for a burn injury and sources of this knowledge among the general population of New South Wales.Design, setting and participants: People aged 16 years or older were interviewed as part of the 2007 NSW Population Health Survey, a continuous telephone survey of NSW residents.Main outcome measure: Weighted proportion of the population with optimal first aid knowledge for burns.Results: In total, 7320 respondents were asked questions related to burn injuries and first aid. Of the surveyed population, 82% reported that they would cool a burn with water, and 9% reported that they would cool the burn for the recommended 20 minutes. Few respondents reported that they would remove the patient’s clothing and keep the injured person warm. The most common sources of first aid information were a first aid book (42%) and the internet (33%). Speaking a language other than English at home, and being over 65 years of age were associated with a lack of first aid knowledge.Conclusions: A minority of people living in NSW know the optimal time for cooling a burn injury and other appropriate first aid steps for burns. This study demonstrates a gap in the public’s knowledge, especially among non-English speaking people and older people, and highlights the need for a clear, consistent first aid message.

Lara A Harvey BSc, MPH · Margo L Barr BSc, MPH · Roslyn G Poulos MB BS(Hons), PhD, FAFPHM · Caroline F Finch BSc, MSc, PhD · Shauna Sherker BSc, MSc, PhD · John G Harvey MB BS, FRACS, FRCS

To the Editor: NSW Health’s latest initiative, www.emergencywait. com.au, is a website that presents real-time information about estimated waiting times at 58 emergency departments (EDs) in New South Wales. Similar websites have been used in other Australian states, including South Australia, Western Australia and Victoria, as well as overseas, in Ontario, Canada, and in Memphis, Tennessee. I am concerned that this initiative will be counterproductive and will add further congestion to our already overcrowded EDs. Extended waiting times are a longstanding problem at EDs. They have traditionally been attributed to staff shortages, delays in pathology and imaging tests,1 and inadequate funding. However, there is another major contributor to waiting times that rarely attracts attention in the lay media — the overwhelming number of patients who inappropriately seek medical attention in EDs and would be better served by a general practitioner. Much of the work in EDs involves treating patients with non-acute and non-urgent problems. Recent examples from my personal experience include a man requesting a prescription for antiepileptic medication, a perimenopausal woman with many months of irregular menstrual bleeding, and a young man with a common cold. All of these patients bypassed their GPs, despite their attendances being within normal business hours. A logical outcome of www. emergencywait.com.au is an increase in the number of non-acute, non-urgent presentations to EDs that are seen to be “quiet”. For alongside each hospital’s estimated waiting time, the website presents a list of nearby hospitals with the number of patients waiting at each, thereby enabling patients to compare EDs and attend the least busy one. Formal studies are scant, but crude American data indicate a 6%–10% increase in ED patient volume since waiting times were publicised.2 Although the transparency of www.emergencywait. com.au may help our EDs to share more equitably the burden of inappropriate patient attendances, I expect that it will increase the overall number of such attendances and ultimately increase waiting times. Australian EDs provide excellent, prompt care for patients who have been in accidents or emergencies, but they are neither equipped nor designed to look after individuals who meet neither of these criteria. The solution to overcrowded EDs lies not in websites that publicise waiting times, but in convincing the public that emergency rooms are for emergencies.

Alexander M Owen

Gambling and diagnostics are related, but strangely reversed, in the way that prior events can affect our clinical judgements The year was 1913; the location, the roulette tables of a Monte Carlo casino. For the previous 10 spins of the wheel, the ball had landed on black. A red was overdue, so the punters began to bet more aggressively against the trend. But the 11th spin produced yet another black number. As did the 12th, and the 13th ... and the longer the run of blacks continued, the more convinced the gamblers became that the subsequent spin would yield a red. Their wagers accelerated. Their losses snowballed. For it was only after 26 consecutive black numbers (by which time few could afford to continue betting) that the streak finally came to an end. It was perhaps the most profitable night in the casino’s history: records were set, fortunes were lost, and the “Monte Carlo fallacy” was born. Also known as the “gambler’s fallacy”,1 it describes the erroneous belief that the outcomes of recent random events have some bearing on future random events. It dictates that if a flipped coin yields 10 consecutive heads, then the likelihood of a subsequent tails is increased, because the coin seems “due” for a tails. Intellectually, we know this law of averages makes no sense: a coin has no memory, so every time it is flipped, there is an equal chance of either side appearing face-up, regardless of what happened on previous flips. Certainly, the odds of flipping heads 10 times in a row are remote — one in 1024, to be exact — yet this number also represents the odds of having any other pattern of heads and tails in a 10-flip series. Although we know this to be the case (undoubtedly, so too did many of the gamblers on that night in Monte Carlo), it is all too tempting to disregard the laws of probability and be seduced by pseudologic. In our clinical practice, it is similarly easy to be fooled by apparent patterns, and unduly influenced by any recent experiences that remain prominent in our minds.2 However, for clinicians, the Monte Carlo fallacy seems to work in reverse: rather than a string of similar events prompting us to think we are “due for a change”, we may instead feel that the “run” is more likely to continue. For example, if, within a short space of time, two patients presenting with hypotension are found to be hypoadrenal, then it may be tempting to look for this unusual diagnosis in all future hypotensive patients, even though other diagnoses may be more common, more likely, and easier to diagnose without expensive investigations. If a patient has a fall while in hospital, and then dies unexpectedly from an unidentified intracranial bleed, we may feel compelled to request a brain scan for any subsequent patient who has such an accident. We may do this even when the patient appears unhurt, and our clinical judgement would otherwise suggest that such a test is not indicated. While the outcome for the first patient was tragic, it in no way affects the likelihood that a second patient’s (unrelated) fall will also have life-threatening complications — just as the first 25 black roulette numbers had no bearing on the outcome of the 26th. Our approach to any clinical situation is guided by the accumulation of our previous experiences, but somehow the most recent ones seem to bear the most weight. Ultimately, we are human, and humans are pattern-seeking creatures. We see faces in amorphous clouds, and stars scattered across the night sky form images before our eyes. And to this pattern-seeking ability we owe much of our understanding of medicine: the linking of infection outbreaks to geographical areas has identified sources of contamination, and the observation of disease trends has revealed unrecognised side effects of drugs. A great deal of our knowledge today has been acquired through observing the unusual, the unexpected and the uncommon, and continuing to do so will certainly teach us more. However, in day-to-day clinical medicine, the old maxim rings true: common things occur commonly.

Alexander M Owen MB BS(Hons), BSc(Med)Hons

Objective: To determine the Australian native ant species associated with ant sting anaphylaxis, geographical distribution of allergic reactions, and feasibility of diagnostic venom-specific IgE (sIgE) testing.Design, setting and participants: Descriptive clinical, entomological and immunological study of Australians with a history of ant sting anaphylaxis, recruited in 2006–2007 through media exposure and referrals from allergy practices and emergency physicians nationwide. We interviewed participants, collected entomological specimens, prepared reference venom extracts, and conducted serum sIgE testing against ant venom panels relevant to the species found in each geographical region.Main outcome measures: Reaction causation attributed using a combination of ant identification and sIgE testing.Results: 376 participants reported 735 systemic reactions. Of 299 participants for whom a cause was determined, 265 (89%; 95% CI, 84%–92%) had reacted clinically to Myrmecia species and 34 (11%; 95% CI, 8%–16%) to green-head ant (Rhytidoponera metallica). Of those with reactions to Myrmecia species, 176 reacted to jack jumper ant (Myrmecia pilosula species complex), 18 to other jumper ants (15 to Myrmecia nigrocincta, three to Myrmecia ludlowi) and 56 to a variety of bulldog ants, with some participants reacting to more than one type of bulldog ant. Variable serological cross-reactivity between bulldog ant species was observed, and sera from patients with bulldog ant allergy were all positive to one or more venoms extracted from Myrmecia forficata, Myrmecia pyriformis and Myrmecia nigriceps.Conclusion: Four main groups of Australian ants cause anaphylaxis. Serum sIgE testing enhances the accuracy of diagnosis and is a prerequisite for administering species-specific venom immunotherapy.

Simon G A Brown MB BS, PhD, FACEM · Pauline van Eeden BAppSci(MLS), PhD · Michael D Wiese BPharm, MClinPharm, PhD · Raymond J Mullins PhD, FRACP, FRCPA · Graham O Solley MB BS, FACP · Robert Puy MB BS, FRACP · Robert W Taylor PhD · Robert J Heddle PhD, FRACP, FRCPA

To the Editor: The number of vulvoplasty or labioplasty procedures rebated by Medicare Australia has more than doubled over the past 10 years;1 in the United Kingdom, a similar trend was observed in the National Health Service (NHS) (Box).2 Recent media debate in Australia highlights this as a concerning problem.3 The community assumes that surgical operations are clinically effective treatments performed for identifiable pathological features. In the context of female genital cosmetic surgery (FGCS), there is a blurring between disease and dissatisfaction, the latter being at least partly informed by cultural pressure about physical appearances. In addition, there is an absence of evidence on clinical effectiveness,4 and an apparent lack of commitment to monitor adverse events. This raises the question of how clinicians justify referring women for FGCS. A recent audit of referral letters for labioplasty in an NHS gynaecology clinic in the UK (University College London Hospitals project no. 03/0173) offers interesting insights. Of the 48 letters reviewed, the mean age of the women referred was 25 years (range, 9–50 years). Complaints about genital appearance were identified in 34/48 (71%) of letters (eg, embarrassment about undressing in public changing rooms). Physical discomfort was mentioned in 23/48 (48%) letters (eg, difficulty with activities such as cycling). Sexual problems were mentioned in 21/48 (44%) letters (eg, a reluctance to engage in sexual relationships). In two of the letters, the referrers mentioned disparaging comments by previous sexual partners, and one mentioned harassment by other girls at school. Alarmingly, a further seven letters (15%) alluded to concerns being flagged by the girls’ mothers. Only 77% of referrers reported examining the patient. A third of referrers judged the labia to be “normal”, yet nevertheless requested surgery for their patients. Pejorative language such as “leathery in appearance” or “pendulous and elongated” was used in 12 (25%) of the letters. Medical training may cover basic vulval anatomy, but detailed study of morphology is not included. This knowledge gap would have been less problematic in the past. However, in recent years, where intense marketing of FGCS5 is contributing to soaring demand, medical practitioners may not be sufficiently informed about female genital anatomy to assess and advise women about their concerns. Reasons for the increasing prevalence of female distress about genital appearance are likely to be complex and rooted in social and cultural changes. In the absence of identifiable diseases, referral for operations may not be the most appropriate way of managing women’s body insecurities. Labioplasty and vulvoplasty operations rebated by Medicare Australia1 and covered by the United Kingdom National Health Service2 over the past 10 years* INR = international normalised ratio. * Graph shows abbreviated, not daily, data. Intervals are weekly up to Week 9, then vary according to when INR was measured.

Rebecca Deans · Lih-Mei Liao · Naomi S Crouch · Sarah M Creighton

Cosmetic lid margin tattoo (or cosmetic blepharopigmentation) is increasingly purveyed in Australia by specialist beauty salons and is marketed as a form of permanent make-up. Like other forms of modern tattoo art, it is applied using an electric needle tip which oscillates at 50–150 cycles per second. Each cycle embeds a small amount of pigment into the dermis. Typically, it is performed after application of a topical local anaesthetic. In this case, tattoo pigment was inadvertently embedded directly into the cornea. This resulted in severe conjunctivitis and a large epithelial defect. In this image, taken 1 month after the injury, the anterior corneal stroma remains stippled with tattoo pigment.

Adam K Rudkin · John L Crompton

To the Editor: Grills eloquently informs readers on the dangers of the Easter bunny and chocolate, and reminds us that Easter eggs may pose a choking hazard.1 It is worth noting that the foil used to wrap Easter eggs also poses a health risk. This was demonstrated in the case of a 20-year-old woman who presented to hospital with respiratory distress after inhaling foil wrapping from an Easter egg.2 The foil wrapper had been pushed inside the woman’s salbutamol inhaler by her 2-year-old son and subsequently occluded her left lower lobe bronchus after she used her inhaler.

Mark Naunton

Our health system supports a model of care that is strongly reliant on provision of services in hospital. Two studies reported in this issue of the Journal illustrate the dominance of this model, the increasing demands on the system, and the way that the quality of care provided may be inappropriate for two major groups in our community: the very old and those with terminal disease. An accompanying editorial by Abernethy (→ "Learning health care" for patients and poulations) calls for a patient-focused “learning” health system to facilitate care for these groups. It has long been accepted that the majority of an individual’s health care costs are expended during the last few months of life. However, acknowledging the futility of this has not led to the development of effective alternatives. Little work has previously been done in Australia to examine the delivery of care for seriously ill Australians in their last months of life. The findings of Rosenwax and colleagues in this regard (→ Hospital and emergency department use in the last year of life: a baseline for future modifications to end-of-life care) are bleak, but perhaps not surprising. Of patients in their study who were suitable for palliative care, 70% had at least one visit to the emergency department and 96% were admitted to hospital during their last year of life, with an average of eight admissions and a mean length of stay of 6 days. Most of the admissions and time spent in hospital occurred within the last 3 months of life, and 62% of patients died in hospital. These are all markers of a poor standard of palliative care (J Clin Oncol 2003; 21: 1133-1138), which we accept too readily. Lowthian and colleagues analysed the use of emergency ambulance transport in Melbourne (→ The challenges of population ageing: accelerating demand for emergency ambulance services by older patients, 1995–2015), showing an increasing demand for this service and, by implication, the hospital system, particularly by patients aged 85 years or older. Since 1994–95, the annual rate of emergency ambulance transfers increased by almost 5% beyond what could be explained by population changes. The authors project a further increase in usage to 2014–15 of up to nearly 70%. Although people aged 85 years or older comprised 1.6% of the population in 2007–08, they accounted for 13.6% of emergency transportations. As the authors point out, ambulance transportation most often results in emergency department attendance, with a high rate of subsequent hospital admission. Older patients are more likely to be admitted, and typically for longer, than other age groups. As our population ages, demand for both ambulance and hospital services will rise, and this will need to be factored into health planning. At heart, both these studies identify a need for an alternative model of care. An aggressive-treatment, event-determined and hospital-centred model fails to give appropriate care to the terminally ill and older people who have complex chronic comorbidities. The articles canvass some alternative models, but neither suggests assessing whether good primary care can reduce demand on ambulance and hospital service use. Palliative care and aged care should not primarily be the province of the hospital and the acute health care system, and our continued acceptance of this and of the concentration of health care spending in the last months of life is no longer tenable. It represents both bad care and a waste of money.

Annette Katelaris MB BS, MPH, FRACGP

Objective: To measure the growth in emergency ambulance use across metropolitan Melbourne since 1995, to measure the impact of population growth and ageing on these services, and to forecast demand for these services in 2015.Design and setting: A population-based retrospective analysis of Ambulance Victoria’s metropolitan emergency ambulance transportation data for the period from financial year 1994–95 to 2007–08, and modelling of demand in the financial year 2014–15.Main outcome measures: Numbers and rates of emergency ambulance transportations.Results: The crude annual rate of emergency transportations across all age groups increased from 32 per 1000 people in 1994–95 to 58 per 1000 people in 2007–08. The rate of transportation for all ages increased by 75% (95% CI, 62%–89%) over the 14-year study period, representing an average annual growth rate of 4.8% (95% CI, 4.3%–5.3%) beyond that explained by demographic changes. Patients aged ≥ 85 years were eight times (incident rate ratio, 7.9 [95% CI, 7.6–8.3]) as likely to be transported than those aged 45–69 years over this period. Forecast models suggest that the number of transportations will increase by 46%–69% between 2007–08 and 2014–15, disproportionately driven by increasing usage by patients aged ≥ 85 years.Conclusions: These findings confirm a dramatic rise in emergency transportations over the study period, beyond that expected from demographic changes. Rates increased across all age groups, but more so in older patients. In the future, such acceleration is likely to have major effects on ambulance services and acute hospital capacity. This calls for further investigation of underlying causes and alternative models of care.

Judy A Lowthian MPH, BAppSc(SpPath), LMusA · Damien J Jolley MSc(Epidemiology), MSc, AStat · Andrea J Curtis BSc(Hons), PhD · Alexander Currell BE, BA, MEngSc · Peter A Cameron MB BS, MD, FACEM · Johannes U Stoelwinder MD, FRACMA, FACHSE · John J McNeil MB BS, PhD, FRACP

Objectives: To describe the characteristics of patients with burn injury admitted to a major trauma hospital in Melbourne following the Black Saturday bushfires of 7 February 2009, and to provide a detailed analysis of the hospital’s response to the crisis.Design, setting and participants: A retrospective chart review of ambulance and hospital records of patients admitted to the Victorian Adult Burns Service (VABS) at The Alfred Hospital (The Alfred) following the bushfires.Main outcome measures: Patient characteristics and outcomes: age, sex, total and full thickness body surface area burnt, type and site of burn, hospital and intensive care unit length of stay (LOS) and receipt of standard burn care practices. Estimated glomerular filtration rate, theatre time and LOS data for the bushfire cohort compared with corresponding data for historical cohorts from VABS and from a similar institution in New Zealand.Results: Nineteen patients were admitted to VABS over the first 48 hours after the bushfires. Of these, nine patients were subsequently admitted to The Alfred’s intensive care unit. Most patients (74%) were men with a mean age of 52.7 years (SD, 12.4 years). Seventeen patients (89%) underwent at least one surgical procedure, which resulted in 4355 minutes of theatre time for the bushfire cohort in the first week. Hospital LOS was similar for the bushfire and New Zealand cohorts. Compared with the VABS historical cohort, there was a higher incidence of abnormal renal function among the bushfire cohort patients.Conclusions: Although relatively few patients with severe burns were admitted to VABS, significant increases in resource allocation were required to manage them in terms of additional theatre time, consumables and staffing. The experience of VABS may aid planning for future mass burns casualty events.

Heather J Cleland MB BS, FRACS · David Proud MB BS · Anneliese Spinks PhD · Jason Wasiak MPH

Medical Assessment Units (MAUs) provide an opportunity for multidisciplinary staff to manage recently admitted acutely unwell patients with complex medical illnesses. We propose concerted development of robust mechanisms for identifying and managing patients whose condition is unstable as they move through hospital departments. Track, trigger and response (TTR) systems (eg, medical emergency team calls and early warning scores) have been introduced to hospital practice, but evidence for their effectiveness is, so far, incomplete. The current variation in TTR systems within and between hospitals impairs intersite comparisons. A range of outcome measures, including risk of physiological deterioration, mortality and projected hospital length of stay, could be usefully investigated by future intersite collaborative research. More deliberate, systematic, evidence-based design of “response” in TTR systems may help in identifying patients who need early attention from skilled medical staff. We need more uniform TTR systems, more research on TTR systems and more multisite research; MAUs are ideally situated to address this important area.

Paul F Jenkins MB BChir, FRCPE, FRACP · Campbell H Thompson MD, DPhil, FRACP · Lorna L Barton MB BS, MRCP

To the Editor: I refer to the article by Cameron and Cooke,1 and the letter from Forero and colleagues.2 Cameron and Cooke correctly identified key problems associated with using a time-based process standard as a solution to poor patient outcome linked to overcrowding in emergency departments (EDs). They highlighted the need for monitoring to ensure “patient safety and quality of care are not compromised at any stage of the emergency pathway”. Forero et al challenged their assertion that the United Kingdom has replaced the 4-hour rule, and suggested there are three new time-based measures used as indicators of performance. Unfortunately, Forero et al have not noted the critical difference in new UK policies, in which no specific time cut-off is used as the benchmark for good performance.3 While acknowledging the importance of timeliness of care, “clinical outcomes and the experience of the patient” will be the focus of emergency care in the UK under the new Department of Health initiative effective April 2011.4 Surely Andrew Lansley’s (UK Secretary of State for Health) statement that “the four hour standard should be abolished”5 must mean nothing else but complete abandonment of this standard!. Concerns regarding a time-based performance indicator (and funding) were previously illustrated by Nocera in this Journal, who showed that numerical key performance has been a primary motivation for data fraud in Victoria and New South Wales, relating to ED waiting time.5 Furthermore, there is a possibility of admitting an unprepared patient to a ward at 4 hours,6 without acceptance of care by specialist team. A patient not properly worked up and sent to ward will not have the same automatic privileged access to critical care staff ratios or fast-tracked requests for pathology or radiology investigation provided in the ED. This can contribute to the excessive length of stay and, indirectly, hospital bed block. I caution against overly enthusiastic support for the 4-hour rule being instituted in Australian hospitals as a panacea to access block in the ED, and stress the need for better discharge planning, experienced patient flow and bed management, and improved hospital staff rostering for after hours. The latter include rethinking of ED doctors’ 24-hour staffing, with ED specialists attending to patients primarily,7 and junior doctors as assistants (if a 4-hour standard is to be attained), especially when facing an imminent glut of junior doctors, who will require close supervision, rotating through the ED.8

Shyan L Goh

We report a case of compassionate use of a haemoglobin-based oxygen carrier in a severely injured Jehovah’s Witness patient, for whom survival was considered unlikely. Severe anaemia and cardiac hypoxia were reversed after slow infusion of this agent. No vasoactive side effects were associated with the treatment, possibly due to the slow infusion, and the patient survived. (MJA 2011; 194: 471-473) Clinical recordA healthy 32-year-old woman was a passenger in a vehicle involved in a high-speed collision with a truck, and she was entrapped for 2 hours. Initially, her heart rate was 100 beats/min, blood pressure was 90/50 mmHg, respiratory rate was 28 breaths/min and oxygen saturation measured by pulse oximetry (SpO2) was 92% on air. Her Glasgow Coma Scale score was 9 (eye opening, 2; verbal response, 1; motor response, 6) and her pupils were equal and reactive to light. Her family indicated that she was a Jehovah’s Witness and would not accept the units of blood that had been transported to the accident site. Paramedics performed endotracheal intubation, immobilisation, left femoral splinting and resuscitation with a 7000 mL crystalloid infusion, and applied dressings to wounds. The patient was transported by helicopter to The Alfred’s trauma centre. On arrival at the trauma centre, she was ventilated, her heart rate was 120 beats/min, blood pressure was 62/26 mmHg and SpO2 was 79% on 100% fraction of inspired oxygen (FiO2). Following discussions with the family, the trauma team agreed not to treat the patient with packed red cells, platelets or fresh frozen plasma. Thoracostomies for a right tension pneumothorax and a left pneumothorax were performed, which increased her blood pressure to 105/65 mmHg and SpO2 to 100% on FiO2 100%. Intercostal drains were inserted and connected to a cell salvage device. She was administered 1400 mL of succinylated gelatin, 10 units of cryoprecipitate and 5 mg of recombinant factor VIIa. Bleeding was controlled with direct pressure, and a scalp wound was closed. Ultrasonography demonstrated a moderate pericardial effusion with systolic right ventricular collapse and free intraperitoneal fluid. Electrocardiography demonstrated sinus tachycardia with no ST segment changes. Initial blood tests showed a haemoglobin (Hb) level of 67 g/L (reference range [RR], 113–159 g/L), activated partial thromboplastin time of 44.3 s (RR, 26–38 s), international normalised ratio of 1.9 (RR, 1.0–1.3), serum fibrinogen level of 3.2 μmol/L (RR, 5.9–11.8 μmol/L, lactate level of 3.9 mmol/L (RR, 0.6–2.2 mmol/L) and serum creatinine level of 55 μmol/L (RR, 60–105 μmol/L). Imaging showed a fractured right orbit and maxilla, bilateral rib fractures, a grade 4 splenic laceration, a likely jejunal injury with intramural haematoma, a left distal humerus fracture, a comminuted open left femoral shaft fracture, an unstable T12/L1 fracture dislocation (60% off-ended), and multilevel spinous process and transverse process fractures. Laparotomy and fixation of the patient’s thoracolumbar injury were deferred because of the likelihood of associated bleeding. Instead, she underwent splenic embolisation, external fixation of her open left femoral shaft fracture and debridement of her left humerus injury. She received 1000 mL of 4% albumin and 1000 mL of crystalloid fluid during these procedures, and 10 mg of intravenous vitamin K afterwards. On postoperative admission to the intensive care unit, her Hb level was 36 g/L and her coagulation profile was normal. Low-dose noradrenaline was required to support her blood pressure until Day 2. Her urine output over the first 24 hours was 4500 mL. A follow-up transthoracic ultrasound showed abatement of the pericardial effusion. An abdominal computed tomography (CT) scan with oral contrast excluded jejunal injury. To protect renal function, intravenous contrast was not used. Placement of an inferior vena cava filter was deferred because of anatomical distortion secondary to the thoracolumbar injury. Several strategies were used to manage the patient’s anaemia. Sedation minimised metabolic demand. A ventilation cycle of 2 hours of 90% FiO2, followed by 2 hours of 90% SpO2 and then 20 hours of 95% SpO2 was used. This was employed to maximise oxygen delivery while minimising shunt from absorption atelectasis and to promote erythropoiesis. Recombinant erythropoietin (36 000 units daily for 6 days), folic acid (5 mg daily continued until discharge), vitamin B12 (1 mg daily for 6 days) and a single iron infusion of 500 mg were administered to maximise haematopoiesis. Menses was inhibited with progesterone. Blood testing was performed using paediatric-sized samples. Pneumatic calf compressors were applied and regular lower-limb sonography was performed to exclude venous thrombosis. The trauma team considered using a synthetic haemoglobin-based oxygen carrier (HBOC) to increase oxygen delivery to the patient’s tissues. On Day 3, OPK Biotech (Cambridge, Mass, USA), the Therapeutic Goods Administration (TGA), the Australian Quarantine and Inspection Service and airline carriers were contacted to determine availability and import permissions. HBOC-201 was supplied by OPK Biotech without charge. Informed consent for use of HBOC-201 was obtained from the patient’s family. Approval for emergency compassionate use of HBOC-201 was obtained from The Alfred Ethics Committee on Day 4. The published and unpublished in-vivo and in-vitro research into HBOC-201 was reviewed at a multidisciplinary meeting, and its use was agreed to. Ten 250 mL units of HBOC-201 were imported under Category A of the TGA’s Special Access Scheme. By Day 5, the patient’s Hb level had dropped to 29 g/L and her serum troponin I level was 0.33 μg/L (RR, < 0.10 μg/L), indicating cardiac hypoxia (Box). An electrocardiogram showed widespread ST depression and an episode of non-sustained ventricular tachycardia was documented. Survival with this degree of metabolic demand, the associated anaemia, and resultant end-organ hypoxia was considered unlikely. Following advice from experienced United States physicians, 3 units of HBOC-201 were administered on Day 5, and a further 2 units were administered on Day 6 with ascorbic acid (1 g twice daily continued until discharge). Each unit of HBOC-201 was infused over 8 hours to minimise any adverse effects related to volume overload, vasoactivity or methaemoglobin. Intravenous glyceryl trinitrate was the agreed treatment in the event of hypertension,1 but this was not necessary. After the slow administration of 5 units of HBOC-201, the patient’s Hb level increased from 35 g/L to 62 g/L (Box). Echocardiography performed before and after HBOC-201 treatment showed a reduction in cardiac output from 6.8 L/min to 5.0 L/min. Electrocardiography findings and troponin I levels returned to normal and no further arrhythmias were noted. Somatosensory evoked potentials revealed intact lower-limb neurological pathways. On Day 7, closed reduction was performed and a body cast was applied to treat the T12/L1 fracture dislocation. Imaging showed improved alignment, and an inferior vena cava filter was placed. From Day 6, the patient’s temperature began spiking, secondary to femoral pin site infections and pneumonia. Despite treatment with antibiotics, temperature spiking continued. Cooling was commenced to minimise metabolic demand. A transoesophageal echocardiogram on Day 11 showed right ventricular regional wall motion abnormality but no evidence of endocarditis. A CT scan showed persistent bilateral pneumothoraces, a left pleural effusion and an epidural haematoma at L1 level. Bilateral tube thoracostomies were re-performed and an antifungal was added to the anti-infective regimen. A percutaneous tracheostomy was performed on Day 12. Low-dose heparin therapy for thromboprophylaxis was deferred until Day 17. By Day 21, the infections had resolved and the tracheostomy tube was removed. The femoral and humeral fractures were internally fixed on Day 20 with minimal blood loss. On Day 30, the patient’s Hb level was 107 g/L and operative reduction and internal fixation of her thoracolumbar spine was performed. She was well when discharged to a rehabilitation facility on Day 43 — her cognition was formally assessed as normal, lower-limb neurological pathways were intact and Hb level was 101 g/L. DiscussionWe have described compassionate use of HBOC-201 in a severely injured Jehovah’s Witness patient. To our knowledge, this is the first report to describe reversal of documented cardiac hypoxia secondary to anaemia following trauma. Haemorrhagic shock is responsible for one-third of deaths following high-energy trauma.2 Integrated trauma care systems coordinate rapid haemorrhage control, shock recognition and surgical interventions to minimise blood loss and coagulopathy.3 Healthy volunteers can tolerate Hb levels of 50 g/L without evidence of end-organ hypoxia.4 However, it is estimated that the median Hb concentration associated with mortality is about 25 g/L.5 During the phase of increased metabolic demand in our patient, there was evidence of cardiac hypoxia when her Hb level reached 29 g/L. This prevented further operative interventions and placed her at high risk of cardiac dysrhythmias and death. HBOC-201 is a modified lactated Ringer’s solution containing 130 g/L of polymerised Hb of bovine origin. It is compatible with all blood types, stable for 3 years when stored at 2–30°C and stable for 2 years when stored at 40°C. When fully saturated, HBOC-201 has the same oxygen-carrying capacity as whole blood with the same Hb concentration. The partial pressure of oxygen at which HBOC-201 is 50% saturated (40 mmHg) is higher than that for cellular Hb (27 mmHg), which facilitates oxygen delivery to tissues. The half-life of HBOC-201 is approximately 20 hours.6 Polymerisation of the Hb reduces its glomerular diffusion and nephrotoxicity. A potential complication of HBOC-201 administration is hypertension and increased left ventricular afterload. Infusing each unit slowly (over 8 hours) in our patient may have diminished any vasoactive side effects. Two case reports of using HBOC-201 to treat severe anaemia following blunt trauma have been published. The first described improved cerebral oxygen delivery, but not survival, in a patient with head injuries.7 The second described successful reversal of haemorrhagic shock in a patient whose Hb level dropped to 45 g/L before HBOC-201 administration.8 However, the lack of clear HBOC-201 transfusion indications and end points, as well as the lack of data to support widespread use of HBOCs, has been criticised.9 A meta-analysis of data from HBOC trials has demonstrated an increased incidence of myocardial infarction and death in anaemic patients without life-threatening haemorrhagic shock.10 However, the analysis did not address the issue of “risk versus benefit” for use of these agents, including HBOC-201, in cases where blood transfusion for severely anaemic patients is not possible. A subsequent series of 54 consenting non-trauma patients with a median Hb level of 40 g/L demonstrated improved chances of survival with no serious adverse events following HBOC-201 administration.11 When blood transfusion is not possible, HBOCs can sustain oxygen delivery to hypoxic tissues.12 Such treatment may represent a life-saving intervention for patients with acute anaemia.13 Interest in safe and effective red blood cell substitutes for oxygen transport is increasing. Agents such as HBOC-201 show particular promise and could make a large difference to survival of trauma patients when blood is not accessible, available or acceptable. Haemoglobin and troponin I levels of a woman who was treated with a haemoglobin-based oxygen carrier (HBOC) following severe trauma * Troponin I levels were measured using the Architect i2000 immunoassay analyser (Abbott Diagnostics, Abbott Park, Ill, USA).

Mark C Fitzgerald MB BS, FACEM · Julie Y Chan MB BS(Hons), BMedSci · Andrew W Ross MB BS, FANZCA · Susan M Liew MB BS(Hons), FRACS(Orth) · Warwick W Butt MB BS, FCICM, FRACP · David Baguley MB ChB, BSc(Hons) · Hatem H Salem MB BS, FRACP · Matthias K Russ Orthopaedic and Trauma Surgeon (Germany) · Conor Deasy FACEM, FCEM, MB BCh BAO · Katherine E Martin MB BS, BMedSci, FRACS · Joseph K Mathew MB BS, MS · Jeffrey V Rosenfeld FRACS, FRCS(Edin), FACS

Visual field defects typically caused by lesions in the optic nerve or optic chiasm may be caused indirectly by subdural haematomas. A 61-year-old man survived transtentorial herniation caused by subdural haematomas that resulted from shaking his head in an attempt to remove a cockroach impacted in his external auditory canal. Bilateral incomplete posterior cerebral artery infarction of both inferior tips of the occipital lobe resulted in bilateral superior quadrantanopia. There are no previous reports of tentorial herniation causing this permanent outcome. (MJA 2011; 194: 420-422) Clinical recordA 61-year-old man presented to the emergency department with a 3-day history of worsening headache and drowsiness. He had a past medical history of renal calculi and gout and was not taking any regular medication. He had a history of consuming 5–6 standard units of alcohol per day, but no antecedent falls or head injury were reported. On physical examination, his Glasgow Coma Scale (GCS) score was 15/15 and his vital signs were normal, apart from mild hypertension (154/80 mmHg). His right pupil measured 4 mm, and his left pupil, 3 mm. His reflexes were documented as brisk in the upper limbs. Results of liver and coagulation studies were normal. A cerebral computed tomography (CT) scan showed large bilateral frontoparietal subdural haematomas (Box 1, A). The right-sided haematoma had mixed hyperdense and isodense areas suggestive of acute on subacute bleeding, while the left frontal haematoma was isodense. The CT scan also showed marked mass effect (Box 1, B) and early tentorial herniation of the uncus (Box 1, C) without tonsillar descent. There was a delay of 8 hours, including transfer of the patient to a neurosurgery centre, before surgery. The patient’s medical notes showed that before undergoing surgery he had developed bilateral extensor Babinski responses and had a GCS score of 14/15. One hour before the operation, the nursing records indicated “GCS 13/15, patient too drowsy and disoriented to consent [to surgery]”. No further imaging was undertaken and no further notes were made before surgery. The patient made an uneventful recovery after bilateral craniotomy and drainage. A CT scan of the brain on discharge about a week later confirmed evacuation of the haematomas and normalisation of brain position. During routine follow-up 10 weeks later, the patient reported persistent difficulty with reading since the operation and that he was experiencing problems differentiating colours. His visual acuity was found to be 6/5 in the right eye and 6/18 in the left, with symptoms of defective colour vision (3/14 Ishihara plates correctly identified with the right eye, and 4/14 with the left). A minor cataract was found in his left eye, but there was no other intraocular abnormality in either eye. His optic discs appeared healthy without pallor in both eyes (and remained so on further follow-up several years later). Computerised visual field perimetry testing conducted at 10 weeks showed bilateral superior altitudinal defects (Box 2). Routine visual evoked potentials showed normal latencies. However, multifocal visual evoked potentials showed normal latencies with decreased amplitude in superior fields bilaterally. Magnetic resonance imaging (MRI) of the brain and orbits conducted 6 months after the surgery showed chronic infarction involving the inferior tip of both occipital lobes medially, more marked on the right side (Box 1, D and E). There was evidence of residual blood products from the evacuated bilateral subdural haematomas, with no evidence of new bleeding. There was no abnormality of the optic nerves or optic chiasm, and venous drainage on magnetic resonance venography was normal. Upon further questioning at this time, a reason for the apparent spontaneous subdural haematomas became evident. The patient described an incident 7 weeks before admission when he awoke with an insect inside his ear. Despite, in his words, “shaking my head from side to side and banging on the side of my head with my fist”, the patient was not able to get the insect out. He was seen at the emergency department, where his ear was syringed and, eventually, a German cockroach (Blatella germanica) was removed with further shaking of the head (which was documented in the hospital records). He recalled a marked headache for the next 2 weeks, which gradually subsided. Recurrence of the headache 5 weeks later prompted him to present to the emergency department again, and the subdural haematomas were detected. DiscussionThis is an unusual and to the best of our knowledge a novel case of bilateral visual field defects related to earlier impaction of a cockroach in the external auditory canal. Subdural haematoma is an uncommon cause of bilateral homonymous hemianopia.1 It can occur as the result of direct local injury to the occipital lobes, or alternatively, mass effect from subdural haematoma can result in tentorial herniation, potentially compromising the blood supply of the posterior cerebral artery (PCA) and placing the regions it supplies at risk. Visual field defects as a consequence of this indirect effect of subdural haematoma have been reported in some surviving patients, but posterior cerebral infarction is more commonly recognised in postmortem examinations of the brain.2-4 Altitudinal visual field defects are typically due to optic nerve lesions and are usually unilateral. Theoretically, the minimal lesion required to produce a bilateral superior quadrantanopia is one located in the inferior optic chiasm; however, this occurs rarely. Typically, injury causes splaying of the chiasm, which is more commonly associated with bitemporal hemianopia. Transtentorial herniation is a well recognised cause of uncal and brainstem displacement and third cranial nerve palsy, but it can also cause stretching and compression of the PCA — thereby compromising the blood supply and leading to infarction.4,5 Survival from tentorial herniation with residual bilateral homonymous hemianopia has been occasionally reported in the literature.6-9 To date, there is no documentation of it causing bilateral superior quadrantanopia. The regions of the brain at risk secondary to PCA ischaemia or infarction are the inferior and medial temporal and occipital cortices. The actual area of involvement depends on which tributaries (and distributions) are affected. The calcarine branch of the medial occipital artery, which supplies the medial occipital lobe, is most commonly involved.10,11 In our patient, there was evidence of mass effect and tentorial herniation secondary to the enlarging subdural haematoma. This would have placed the PCA blood supply at risk. The MRI findings of bilateral infarction of the inferior tip of the medial occipital lobe, together with field test findings of bilateral superior altitudinal defects, confirm the involvement of the visual cortex, which is topographically organised with the cortical representation of the superior field localised inferiorly.5,12 The affected region corresponds to the striate cortex and most posterior part of the prestriate cortex. Both areas are involved in aspects of colour visual processing, suggesting an explanation for the patient’s defective colour vision despite a normal optic chiasm and optic nerves, although a congenital cause cannot be excluded.13 The patient’s history of daily alcohol consumption may have predisposed him to bleeding tendencies and subdural haematomas, although results of his liver and coagulation studies were normal. A diagnosis of acute on subacute subdural haematoma fits well with the timing of the patient’s violent attempts to remove a foreign body from his ear about 7 weeks previously, and with subsequent delayed re-bleeding and increasing supratentorial pressure resulting in uncal herniation and infarction of the part of the primary visual cortex known to correlate with the superior visual fields. A preferred method of removing a cockroach from the ear canal is to drown it with non-toxic vegetable or mineral oil so it can then be easily extracted with forceps. Cautious suction can also be used, taking care not to cause barotrauma by occluding the canal. Lignocaine 2% also rapidly kills the insect or results in it leaving the canal, but entry of lignocaine through any perforation into the middle ear can produce severe sustained vertigo with nystagmus for some hours.14-17 1 Initial computed tomography scan of the brain (A–C), and magnetic resonance images 6 months later (D, E) A: Isodense subdural haematomas (arrows) extending over the convexities longitudinally with effacement of sulci. B: Right hyperdense frontal acute component of a subdural haematoma (arrows) consistent with delayed re-bleeding. C: Uncal herniation, particularly on the left (arrow). D, E: Sagittal fluid-attenuated inversion-recovery magnetic resonance image 6 months later, left and right of midline, respectively (arrows), showing inferior occipital pole infarction. 2 Computerised visual field perimetry of the right eye (A) and left eye (B) The left superior and right superior visual fields are abnormal for both eyes (black areas). The left superior quadrant is slightly worse for both eyes, suggesting this is homonymous and that the lesion is posterior to the chiasm. We describe this as a bilateral superior quadrantanopia rather than a hemianopia to distinguish this circumstance from the normally lateral hemianopias, and because the lesion required to cause this finding is bilateral.

Wan Yi Ng BBus, MB BS · Brian E Chua MB BS, BSc, MPH · Todd A Hardy MB BS, PhD · David Wechsler MB BS · Stephen W Reddel MB BS, PhD

Renal tubular acidosis is an underreported complication of ibuprofen misuse, and can result in life-threatening hypokalaemia. We describe four patients who presented with profound hypokalaemia and muscle weakness associated with excessive ibuprofen ingestion. Ibuprofen cessation and supportive management resulted in complete biochemical resolution within a few days. These cases remind practitioners about potential complications of unmonitored use of over-the-counter analgesics, including those with potential for misuse due to their codeine content. (MJA 2011; 194: 313-316) Clinical recordsPatient 1A 32-year-old woman presented to the emergency department with a 2-day history of evolving paralysis associated with profound hypokalaemia (potassium, 1 mmol/L; reference range [RR], 3–5 mmol/L). She also had epigastric pain without diarrhoea or vomiting and a past medical history of depression, iron deficiency anaemia, chronic constipation, migraines, cigarette smoking and previous intravenous drug use. Family history was unremarkable. Her only medications were citalopram 20 mg daily and a combination of ibuprofen (200 mg) and codeine phosphate (12.8 mg) for migraines. She denied taking laxatives, diuretics, alcohol or illicit drugs. On examination, the patient weighed 38 kg (body mass index, 14 kg/m2), her blood pressure was 90/55 mmHg, and other vital signs were normal. There was generalised flaccid weakness (graded 3/5) with normal sensation. She also had epigastric tenderness. Results of initial laboratory investigations (Box 1) were consistent with distal renal tubular acidosis (dRTA). An electrocardiogram (ECG) demonstrated features of hypokalaemia, including widespread ST-segment depression and U waves. Endoscopy revealed oesophageal erosions and a benign gastric ulcer. An abdominal computed tomography scan demonstrated enlarged, oedematous kidneys without nephrocalcinosis. The patient’s husband revealed she had been consuming the combination ibuprofen–codeine over a prolonged period — at least 25 tablets (5.0 g of ibuprofen) per week and up to 20 tablets in 1 day. Ibuprofen toxicity explained both the gastrointestinal symptoms and the biochemical manifestations of dRTA. No alternate explanation for dRTA was found. The ibuprofen–codeine combination was ceased, and intravenous potassium chloride (KCl) was administered (610 mmol at 5–10 mmol/h over 5 days), with concurrent oral replacement of 64 mmol potassium/day. No signs of opioid withdrawal were detected. Within 5 days, her serum potassium level stabilised at 4 mmol/L and bicarbonate levels normalised without bicarbonate supplementation. She was discharged 3 weeks later on a regimen of 16 mmol of potassium daily; her serum potassium level at discharge was 5 mmol/L. Patient 2A 37-year-old man presented with 3 days of progressive muscle weakness. He had been taking ibuprofen–codeine for several years, with a daily dose of 24 tablets (4.8 g ibuprofen). He was a smoker and denied taking any other medications. There was no history of diarrhoea or vomiting, and family history was unremarkable. He had proximal muscle weakness (graded 3/5) with hyporeflexia and muscle tenderness, but sensation was preserved. Initial investigation revealed a very low serum potassium level (2 mmol/L) and biochemical features consistent with dRTA (Box 1). The ibuprofen–codeine was ceased, and intravenous KCl was administered for 4 days (10–30 mmol/h) with 112 mmol of oral potassium/day. The weakness resolved after 2 days. Oral sodium bicarbonate supplementation (2520 mg/day for 9 days) contributed to normalisation of serum bicarbonate levels. Symptoms of overt opioid withdrawal developed on Day 3 and buprenorphine treatment was commenced. He was discharged on Day 9 after cessation of potassium and bicarbonate supplements, with a serum potassium level of 4 mmol/L. Patient 3A 45-year-old woman, with a remote history of intravenous drug use, presented after 7 days of lethargy and anorexia. She had multiple dental caries, and for several months had ingested 9.6–14.4 g/day of ibuprofen (about 50 tablets per day). She took no other medications and had an unremarkable family history and physical examination. Initial investigations revealed hypokalaemia (potassium, 2 mmol/L) with acute kidney injury, renal potassium wasting and biochemistry consistent with dRTA (Box 1). Gastroscopic investigation of microcytic anaemia found gastric antral ulceration with a peptic oesophageal stricture. No cause for RTA other than ibuprofen overdose was found. Ibuprofen was ceased, and intravenous sodium bicarbonate and KCl (220 mmol over 3 days at a maximum rate of 10 mmol/h) were administered. Concurrent oral potassium replacement occurred at 60 mmol/day. On discharge, 5 days later, renal function was normal and the serum potassium level was 3 mmol/L. Patient 4A 40-year-old man presented with a 2-day history of profound generalised weakness associated with hypokalaemia (potassium, 1 mmol/L). He had consumed 1.4–2.0 g/day of ibuprofen for 3 months for degenerative back pain. There was no history of diarrhoea or vomiting, he took no other medications and had no significant family history, and he was a smoker. The patient had normal vital signs apart from bradycardia (50 beats/min), with generalised flaccid weakness (graded 1–2/5) with preserved reflexes and sensation. An ECG demonstrated sinus bradycardia with prolonged QTc interval and U waves. Initial biochemistry results (Box 1) were consistent with RTA. Although the urine pH of 6.5 was higher than expected for the low serum bicarbonate level (11 mmol/L), proximal RTA (pRTA) was diagnosed in view of the negative urine anion gap and findings suggesting proximal tubular dysfunction. These included hypouricaemia (0.18 mmol/L; RR, 0.20–0.42 mmol/L), hypophosphataemia (0.40 mmol/L; RR, 0.8–1.5 mmol/L) and mild proteinuria. As there were no features suggesting alternative causes for pRTA, ibuprofen was considered the most likely causative factor, and was discontinued. Intravenous potassium (1010 mmol over 3 days at a maximum rate of 20 mmol/h), bicarbonate (total dose, 500 mmol) and phosphate (total dose, 50 mmol) were administered under electrocardiographic monitoring. The patient’s muscle strength improved within 24 hours and he was discharged 4 days later with a serum potassium level of 3 mmol/L. Potassium supplementation was ceased on discharge. DiscussionIbuprofen, a non-steroidal anti-inflammatory drug (NSAID), is widely used and readily available over the counter (OTC). Excessive ingestion of ibuprofen, in combination with codeine or alone, can result in ibuprofen toxicity, including RTA. In Australia, the maximum quantity of ibuprofen–codeine available OTC has recently been reduced from 72 to 28 tablets due to problems related to codeine misuse. We have described four patients with profound hypokalaemia due to ibuprofen-induced RTA. This is an underreported complication, which may present with hypokalaemic paralysis. Three of the patients were admitted to the same tertiary care hospital within 3 months of each other. The remaining patient was admitted to a peripheral hospital the previous year. In each case, the differential diagnosis of hypokalaemia initially included transcellular potassium shift, renal potassium wasting and gastrointestinal losses. Medication histories were uniformly negative for drugs known to cause intracellular potassium movement. Thyroid function was normal and there was no family history of hypokalaemic periodic paralysis. Urinary potassium wasting was documented in all cases by excessive urine potassium excretion (> 20 mmol/day or spot urine potassium > 20 mmol/L) in the presence of hypokalaemia.1 This was not explained by diuretic use or magnesium deficiency. The hyperchloraemic metabolic acidosis and non-acidified urine pH were in keeping with RTA. Gastrointestinal potassium and bicarbonate loss was unlikely in the absence of diarrhoea or laxative use. In two cases, gastric ulceration provided corroborative evidence for ibuprofen toxicity. Investigations found no alternative aetiology for RTA (Box 2). Ibuprofen cessation and supportive therapy allowed complete biochemical resolution within days. Unfortunately, no follow-up information could be obtained to ascertain whether the RTA was recurrent, or whether a previously unrecognised aetiology for RTA had become apparent. Characteristics of RTA are summarised in Box 3. Renal acidification is impaired, resulting in a hyperchloraemic metabolic acidosis.2 Hypokalaemia due to kaluresis is a feature of both proximal and distal RTA. Multiple factors contribute to hypokalaemia. Metabolic acidosis impairs proximal sodium reabsorption, leading to increased distal sodium delivery, secondary hyperaldosteronism and increased potassium secretion.3 In distal RTA, impaired hydrogen ion excretion promotes potassium loss in exchange for sodium to maintain electroneutrality. Reduced H–K-ATPase pump activity results in reduced distal potassium reabsorption.4 Four previously published case reports5-8 have described similar clinical presentations occurring with ibuprofen use of 4.8 to 28 g per day. However, one of our patients (Patient 4) developed RTA at a dose below the maximum recommended. No other NSAID has yet been implicated with this complication. The mechanism by which ibuprofen induces RTA is unknown. Other nephrotoxic effects of NSAIDs, including acute and chronic kidney injury, interstitial nephritis and nephrotic syndrome, result from impaired synthesis of cytoprotective prostaglandins, a consequence of cyclo-oxygenase-1 (COX-1) inhibition. It is hypothesised that the pathogenesis of ibuprofen-induced RTA may involve carbonic anhydrase (CA) inhibition. CA catalyses the interconversion between carbon dioxide and bicarbonate and is crucial to renal acid–base regulation. It is present in renal proximal tubules and collecting ducts as well as a variety of other tissues, including bone, brain and gut.9 Congenital CA deficiency is characterised by proximal and distal RTA, osteopetrosis and cerebral calcification.10 High titres of an auto-antibody directed against CA II have been noted in some patients with dRTA associated with Sjögren syndrome.11 Induction of these auto-antibodies has resulted in the development of RTA in a mouse model of Sjögren syndrome.12 Other NSAIDs including aspirin13 and flurbiprofen14 have been shown to have CA-inhibitory activity in vitro. More recently, celecoxib and valdecoxib, which are COX-2 selective NSAIDs, have been demonstrated to be potent inhibitors of CA due to binding of their sulfonamide moiety to its zinc (Zn2+) ion.15 Although ibuprofen lacks a sulfonamide moiety, it can inhibit human and bovine erythrocyte CA II.14 CA inhibition would be consistent with our observations of both proximal and distal RTA. In conclusion, profound hypokalaemia due to RTA is a potentially fatal complication of ibuprofen use. Although it usually occurs with excessive doses, it can occur at doses below the maximum recommended. The pathogenesis is unknown but may involve CA inhibition. Opioid addiction with deliberate misuse of ibuprofen–codeine analgesics is common.16 Therefore, ibuprofen toxicity should be considered in the differential diagnosis of patients presenting with severe hypokalaemia or hypokalaemic paralysis. 1 Baseline laboratory investigations and other characteristics of four patients with ibuprofen-induced renal tubular acidosis Reference range Patient 1 Patient 2 Patient 3 Patient 4 Sex, age in years Female, 32 Male, 37 Female, 45 Male, 40 Ibuprofen dose* 0.6–4.0 g/day 4.8 g/day 9.6–14.4 g/day 1.4–2.0 g/day Other medications Citalopram 20 mg/day; no complementary medicines, laxatives, diuretics or illicit drugs No prescription medicines, laxatives, diuretics or illicit drugs No other prescribed or over-the-counter medicines No other prescribed, over-the-counter or complementary medicines, diuretics or laxatives Serum pH 7.32–7.43 7.26 7.28 7.16 (venous) 7.27 Pco2, mmHg 37–50 21 32 22 27 HCO3-, mmol/L 22–32 10 14 8 11 Anion gap 7–17 10 8 16 15 Na+, mmol/L 134–146 141 140 134 141 Cl-, mmol/L 98–108 122 120 112 116 Urea, mmol/L 3.8 3.9 5.4 18.0 6.0 Creatinine, μmol/L 60–110 106 83 222 83 K+, mmol/L at presentation 3–5 1 2 2 1 K+, mmol/L on discharge 3–5 5 4 3 3 Urine pH 6.5 6.9 6.5 6.5 Na+, mmol/L 63 49 35 42 K+, mmol/L 25 25 22 25 Cl-, mmol/L 85 69 32 78 Anion gap 3 5 25 − 11 Pco2 = partial pressure of carbon dioxide. HCO3- = bicarbonate ion. Na+ = sodium ion. Cl- = chloride ion. K+ = potassium ion. * Maximum recommended: 3.2 g/day. 2 Causes of renal tubular acidosis (RTA)1 Causes of proximal RTA Primary Secondary With Fanconi syndrome (eg, multiple myeloma, light chain disease) Drugs and toxins (acetazolamide, outdated tetracycline, aminoglycosides, sodium valproate, 6-mercaptopurine, streptozotocin, iphosphamide, lead, cadmium, mercury) Associated with other clinical entities (vitamin D deficiency, hyperparathyroidism, chronic hypocapnia, cyanotic congenital heart disease, medullary cystic kidney disease, Alport syndrome, corticoresistant nephrotic syndrome, renal transplantation, amyloidosis, recurrent nephrolithiasis) Causes of distal RTA Primary Secondary Autoimmune diseases (eg, systemic lupus erythematosus, Sjögren syndrome, chronic active hepatitis, primary biliary cirrhosis, thyroiditis, fibrosing alveolitis, rheumatoid arthritis) Drugs and toxins (amphotericin B, lithium, toluene, amiloride, trimethoprim, pentamidine, vanadium) Calcium disorders (eg, primary hyperparathyroidism, vitamin D intoxication, idiopathic hypercalciuria with nephrocalcinosis) Dysproteinemic syndromes (hypergammaglobulinemia, amyloidosis, cryoglobulinemia) Renal diseases (eg, renal transplant rejection, medullary sponge kidney, obstructive and reflux nephropathy) Liver disease (hepatic cirrhosis) Genetic diseases (eg, osteopetrosis, sickle cell disease, Ehlers–Danlos syndrome) 3 Characteristics of renal tubular acidosis (RTA)1 Distal RTA (type 1) Proximal RTA (type 2) RTA type 4 Primary defect Impaired distal H+ excretion Impaired proximal HCO3 2 reabsorption Decreased aldosterone secretion or effect Plasma potassium Usually reduced (hyperkalaemic forms exist) Reduced Increased Urine pH > 5.5 Variable: usually > 5.5 if plasma HCO3- > 16mmol/L; < 5.5 if plasma HCO3- < 16 mmol/L < 5.5 Urine anion gap Positive Negative Positive Nephrocalcinosis Common Rare Rare Other tubular defects Rare Common (generalised proximal tubular dysfunction) Rare H+ = hydrogen ion. HCO3 - = bicarbonate ion.

Jennifer L Ng MB BS(Hons) · David J R Morgan MB BS, DCH, DRANZCOG · Nelson K M Loh MB BS, BMedSci, FRACP · Seng K Gan MB BS(Hons), FRACP, PhD · Patrick L Coleman MB, MRCPI, FRACP · Gregory S Y Ong MB BS · David Prentice MB BS, FRACP

To the Editor: Australia is in the process of making the most important change to its health care system since the implementation of Medicare.1 We agree with Cameron and Cooke that there are important lessons for Australia from the implementation of the 4-hour rule in the United Kingdom.2 As in Robert Zemeckis’s 1985 movie classic, Back to the future, the old question of “If I had the opportunity to do something again, what would I have done differently?” applies. We challenge the assumption that Australia is embarking on something that the UK has recently abandoned. The UK has not actually abandoned the 4-hour rule but expanded it into a suite of eight indicators that include three time-based measures, including total time in the emergency department (ED).3 Our concerns are about how the lessons learned by the UK can be applied in Australia in 2011 and beyond. Cameron and Cooke state that “Measurement systems should be in place to ensure that patient safety and quality of care are not compromised at any stage of the emergency care pathway”.2 The systems we have are neither universal nor integrated across the country. We need substantial data infrastructure, including comparable data linkage services across states. Of all the states, Western Australia has the most advanced national data linkage system. Yet even with the most sophisticated data systems in the world, proper impact assessment studies are required. Australia’s evaluation of the changes being made to rules and systems is neither systematic nor well standardised — to be safe and effective, innovation needs to be evaluated in coordinated and systematic ways.4 We also need systems-thinking approaches and simulation technologies to avoid repeating past mistakes. It is important to link theory and data to learn about the complex dynamics of ED patient flow and safety, and understand the consequences of our interventions.5 As suggested by Cameron and Cooke,2 we should focus on real-time, clinically relevant, consistent and comparable quantitative and qualitative data about patients, staff, processes, outcomes and facilities. We must learn to improve daily performance rather than sanction variable outliers. In conclusion, the lessons learned from the 4-hour target are relevant and appropriate for Australia. Cameron and Cooke have highlighted some of the dangers, including those of inadequate measurement.2 We need timely, integrated and linked data and an explicit theory of performance. We should aim to manage the risks by appropriately funded research and implementation strategies to improve this significant policy intervention while maintaining patients’ outcomes, experience and safety, and the timeliness of instigating their care.

Roberto Forero · Geoff D McDonnell · Sally M McCarthy · Peter Nugus · Jeffrey Braithwaite · Kenneth M Hillman · Daniel M Fatovich · David Mountain · Frank F Daly · Gerard J Fitzgerald · Drew B Richardson

Objective: To evaluate an intern educational project, the More Learning for Interns in Emergency (MoLIE) project, designed to increase intern placements in the emergency department (ED).Design, setting and participants: The study was conducted in the ED of the Royal Brisbane and Women’s Hospital, Queensland, in 2008. As well as the usual direct contact with patients, interns had 8 hours per week of “off the floor” structured learning time supervised by consultants. This allowed for an increased number of interns to complete a term in the ED over a 1-year period. The study was evaluated by an intern exit feedback survey and a senior staff survey.Main outcome measures: Numbers of intern placements in the ED; intern satisfaction with the project; senior medical staff satisfaction with interns’ skills and performance assessments.Results: The number of interns completing a term in the ED increased from 65 in 2007 to 90 in 2008. Overall, the 90 interns surveyed were highly satisfied with their training. Most agreed or strongly agreed that the sessions were relevant and covered the right mix of clinical and professional issues. Most of the 12 senior staff surveyed felt that the participating interns performed slightly or much better than interns in previous years, and that their experience as supervisors and overall patient care were improved.Conclusions: The project successfully combined increased intern numbers with educational outcomes that were well perceived by interns and senior staff, without adversely affecting service delivery or supervision workload in the ED.

Victoria A Brazil MB BS, MBA, FACEM · Jaimi H Greenslade BPsych(Hons), PhD · Anthony F Brown MB ChB, FRCP, FACEM

Objective: To assess the accuracy of data linkage across the spectrum of emergency care in the absence of a unique patient identifier, and to use the linked data to examine service delivery outcomes in an emergency department (ED) setting.Design: Automated data linkage and manual data linkage were compared to determine their relative accuracy. Data were extracted from three separate health information systems: ambulance, ED and hospital inpatients, then linked to provide information about the emergency journey of each patient. The linking was done manually through physical review of records and automatically using a data linking tool (Health Data Integration) developed by the CSIRO (Commonwealth Scientific and Industrial Research Organisation). Match rate and quality of the linking were compared.Setting: 10 835 patient presentations to a large, regional teaching hospital ED over a 2-month period (August – September 2007).Results: Comparison of the manual and automated linkage outcomes for each pair of linked datasets demonstrated a sensitivity of between 95% and 99%; a specificity of between 75% and 99%; and a positive predictive value of between 88% and 95%.Conclusions: Our results indicate that automated linking provides a sound basis for health service analysis, even in the absence of a unique patient identifier. The use of an automated linking tool yields accurate data suitable for planning and service delivery purposes and enables the data to be linked regularly to examine service delivery outcomes.

Julia L Crilly BNurs, MN(Hons), PhD · John A O’Dwyer BCompScInfEng(Hons) · Marilla A O’Dwyer BEng(Hons) · James F Lind BS BM, BMedSci, FACEM · Julia A L Peters MB BS · Vivienne C Tippett BA, GradDipPsych, MPH(BiostatEpi) · Marianne C Wallis RN, BSc(Hons), PhD · Nerolie F Bost BNurs, MN · Gerben B Keijzers MB BS, MClinEpi, FACEM

To the Editor: O’Leary and Major1 have opened debate on the issues raised by the New South Wales-wide introduction of the Clinical Excellence Commission Between the Flags (BTF) observation charts, which incorporate escalation thresholds for vital signs and other criteria. In the BTF charts, “yellow” zone criteria trigger a clinical review and “red” zone criteria, a rapid response.2 Evidence shows that deterioration can be recognised early, reducing serious consequences.3,4 O’Leary and Major trialled a subset of the draft BTF paediatric calling criteria in the context of triage in an emergency department, applying them retrospectively and comparing the actual triage decision with the one that would have been made using the BTF criteria alone. They also examined patient disposition for patients falling within the yellow and red zones. They concluded that “the physiological parameters ... are not suitable as a triage tool in the paediatric emergency department, do not replace an experienced triage nurse, and are a poor predictor of disposition”.1 We are not surprised by this conclusion. The Australasian Triage Scale is designed to assess a patient’s urgency based on presenting problem and general appearance, possibly combined with physiological observations.5 Trialling a subset of vital signs, on their own, against the triage process, although interesting, is unlikely to demonstrate a strong correlation in decision making for the following reasons. The BTF vital signs observations are designed for use in the context of a “track and trigger system” in a general ward, to monitor trends, not as a substitute for the triage process. Vital sign observations on their own contribute little to triage decisions. Triage decisions are poor predictors of disposition (eg, up to 67% of triage Category 2 patients are discharged home from the emergency department) (Sydney South West Area Health Service emergency department data for July 2010, for Campbelltown, Liverpool and Royal Prince Alfred hospitals). On their own, we would expect vital signs to be poorer predictors of disposition outcome than triage decisions, which have the benefit of information on presenting problem and general appearance. Context for vital sign observations has a major influence on their interpretation. We recommend that more work be done on the value of the BTF vital signs criteria as a complement, not alternative, to triage processes.

Charles H Pain · Clifford F Hughes · Marino Festa · Jodie Ekholm · Matthew O’Meara

To the Editor: Waxman’s prompt recovery after a stroke was probably a stroke of luck,1 unless perhaps Saint Mary MacKillop was involved. Amid the conflicting evidence on the effect of thrombolysis on recovery in ischaemic stroke, one fact is beyond doubt — thrombolysis gives no greater improvement at 24 hours than placebo.2 It is the various measures of recovery at 3 months, and the risks of adverse outcomes from protocol violations in administering thrombolysis, that are less clear. The European Cooperative Acute Stroke Study III (ECASS III) showed that there is a benefit from administering thrombolysis up to 4.5 hours after stroke onset,3 and the complete Safe Implementation of Thrombolysis in Stroke International Stroke Thrombolysis Register (SITS-ISTR) data showed that this benefit can be reproduced in non-trial hospital practice.4 Simpson and colleagues say that the Australian data support this conclusion, even though outcomes show slightly higher mortality compared with rest-of-world data.5 There are several gaps in that line of reasoning. A modified Rankin score (mRS) of 0–1 (zero or minimal disability) is the standard measure of a good outcome. In ECASS III, an mRS of 0–1 was seen in 52.4% of patients who received thrombolysis compared with 45.1% of patients who received placebo.3 However, the SITS-ISTR data showed an mRS of 0–1 in just 40% of patients treated within 3 hours of stroke onset and 44% of patients treated at 3–4.5 hours.4 This is despite lesser stroke severity (National Institutes of Health Stroke Scale score: 10 in the SITS-ISTR cohort v 11.6 in the ECASS III placebo group), selective patient inclusion, and exclusion of patient data with protocol violations known to give worse outcomes. Achieving a worse result than placebo is hardly evidence for safe and effective use of thrombolysis in normal clinical practice. However, the Australian study presents the data differently, using an mRS of 0–2 and thereby concluding good outcomes in patients with greater disability than is the accepted good outcome measure.5 Rather than providing the actual data and the percentage of patients with good outcomes, a novel measure of odds ratio comparison with rest-of-world data is made. Publishing data in the same format as for the full SITS-ISTR report would allay concerns of what may be unfavourable outcomes compared with clinical trial data. Patients deserve to be told what their likely prognosis will be in hospitals that are less experienced in stroke thrombolysis than The Alfred, where Waxman received world-class stroke care.

Brendon J Smith

In reply: We were delighted to hear of Waxman’s “miraculous” recovery, and admire the world-class standard of stroke care which was delivered at The Alfred.1 The Australian data in the Safe Implementation of Thrombolysis in Stroke (SITS) database up to 2008 included tertiary referral centres and outer metropolitan hospitals, and centres with varying experience of using recombinant tissue plasminogen activator (rt-PA) in clinical practice. There was no difference in outcomes according to experience of the treating centres. We believe that the non-trial clinical data presented in our article are a realistic indication of expected outcomes for all patients receiving thrombolysis for stroke in Australia. The choice of a modified Rankin score (mRS) of 0–2 as an outcome measure in our article was largely dictated by the SITS international analysis. The aim of our study was to compare outcomes in Australia with those in the rest of the world; these were also not significantly different when an mRS of 0–1 was used as an outcome measure (mRS 0–1 at 3 months, 34.6% for Australia v 37.8% for the rest of the world; P = 0.13). The original National Institute of Neurological Disorders and Stroke (NINDS) trial data,2 now more than 15 years old, have been analysed and re-analysed and, arguably, it is time to move on from rehashing the data. However, if one wishes to follow this path, there was in fact a significant difference in improvement at 24 hours between patients in the rt-PA and placebo groups. Smith’s statement that thrombolysis gives no greater improvement at 24 hours than placebo is correct in terms of the proportion of patients with an improvement in National Institutes of Health Stroke Scale (NIHSS) score of 4 or more, but this is a low benchmark and many untreated patients also show a relatively mild improvement at 24 hours. If one considers major neurological improvement (MNI, defined as an improvement in 24-hour NIHSS score of 8 or more), this was seen in a greater proportion of patients in the rt-PA group compared with the placebo group.3 Patients with MNI have a much greater chance of achieving minimal or no disability at 3 months, which is by far the most accepted outcome measure for thrombolytic therapy. This major early recovery is frequently seen in patients who receive rt-PA, and has been termed the “Lazarus effect”. Waxman was fortunate enough to experience this effect — but it occurs far too often with rt-PA in stroke to pass the Catholic Church criteria for a miracle.

Marion A Simpson · Helen M Dewey · Mark W Parsons

Objective: To describe the clinical features and laboratory findings in patients with definite red-bellied black snake (RBBS; Pseudechis porphyriacus) bites, including correlation with results of venom assays. Design, patients and setting: Prospective cohort study of patients with definite RBBS bites, recruited to the Australian Snakebite Project from January 2002 to June 2010. Main outcome measures: Clinical and laboratory features of envenoming; peak venom concentrations and antivenom treatment. Results: There were 81 definite RBBS bites; systemic envenoming occurred in 57 patients (70%) and local envenoming alone occurred in one patient. Systemic envenoming was characterised by local envenoming in 55 patients (96%), systemic symptoms in 54 patients (95%), anticoagulant coagulopathy with a raised activated partial thromboplastin time (aPTT) in 35 patients (61%) and myotoxicity in seven patients (12%). One patient required non-invasive ventilation for severe myotoxicity that resulted in muscle weakness. Three patients developed local ulceration. There were no deaths. Twenty-two envenomed patients (39%) received tiger snake or black snake antivenom, and administration within 6 hours of the bite was associated with normalisation of the aPTT. Eight patients (36%) had immediate hypersensitivity reactions to antivenom, including one case of anaphylaxis. The median peak venom concentration in 37 systemically envenomed patients with serum available was 19 ng/mL (interquartile range, 12–50 ng/mL; range, 3–360 ng/mL), which did not correlate with clinical severity. In 17 patients who received antivenom and had venom concentration measured, no venom was detected in serum after the first antivenom dose, including nine who were given one vial of tiger snake antivenom. Conclusion: RBBS envenoming caused local effects, systemic symptoms, anticoagulant coagulopathy and, uncommonly, myotoxicity. One vial of tiger snake or black snake antivenom appears to be sufficient to remove venom and neutralise reversible effects, but hypersensitivity reactions occurred in over a third of patients.

Andrew Churchman BM BS(Hons) · Margaret A O’Leary PhD · Nicholas A Buckley BMed, FRACP, MD · Colin B Page MB ChB, FACEM, MMedSci(Clin Epi) · Alan Tankel BSc, MB ChB, FACEM · Chris Gavaghan MB BS, FACEM · Anna Holdgate MB BS, FACEM, MMed · Simon G A Brown MB BS, FACEM, PhD · Geoffrey K Isbister BSc, FACEM, MD

An emergency department audit of horse-related injury presentations alerted researchers to a hitherto uninvestigated source of childhood harm: non-equine horses. A search for the term “horse” in the database of the South Australian Injury Surveillance and Control Unit was performed for presentations of horse-related injuries to a paediatric emergency department of an Australian tertiary teaching hospital over a 5-year period. After all equine-related episodes were extracted, the remaining presentations were herded together and conclusions were jumped to. When legitimate science and research technique failed, poetic licence was prevailed upon.

John A Craven BSc(Hons), FRACP, FACEM · Jacquie K Schutz BM BS, FRACP