The law and standards regarding participant consent to medical research, both at national and transnational levels, evolved in parallel with human rights and medical ethics in the aftermath of the second world war. The specific legal and ethical challenges posed by investigating time-critical acute severe illness in patients who lack capacity to consent, has largely been overcome. New Zealand currently lags behind other jurisdictions with broad national consensus recommendations merely awaiting legislation. This paper narrates and reviews this story.

Abstract Summary This chapter covers the roles of airway surface liquid (ASL), the mucociliary escalator, and cough reflex in protecting the respiratory tract in health. The injurious result of certain disease processes and the negative impact of endotracheal intubation and mechanical ventilation on bronchopulmonary clearance are also discussed. Numerous mucolytic agents are currently used in clinical practice to combat these deleterious effects. These work by modifying ASL production, secretion, and composition, and may have an effect on the mucociliary escalator. Since there is a paucity of evidence in this area, their effects are extrapolated from their use in other respiratory conditions.

Background: Since the COVID-19 pandemic began in December 2019 no specific therapy for managing severe complications of infection has emerged, although this is under intensive investigation. Progressive pneumonia and multi-organ complications are managed with supportive care and COVID-19 has a mortality of >50% when ventilatory support is needed.Methods: We implemented a compassionate use protocol for tocilizumab, a humanised monoclonal anti-Il-6 receptor antibody. Patients with severe COVID-19 requiring oxygen or ventilation, and complicated by hyperinflammation and the cytokine release syndrome (CRS) received tocilizumab (8 mg/kg up to a maximum of 800 mg, with the option of a second dose given after 12-24 hours). CRS was defined as having at least three of: D-dimer above the upper limit of normal (ULN), rising C-reactive protein (CRP), ferritin >1000 ng/mL and lactate dehydrogenase (LDH) greater than the ULN.Oral consent for prescription of an off-label medicine was obtained from patients, their next of kin or representative, whenever possible. The treatment protocol adhered to the Monitored Emergency Use of Unregistered and Investigational Interventions of the WHO.Findings: Of seventeen patients with severe COVID-19 seen between 3-12th April 2020, eleven patients (seven ventilated and four receiving high flow oxygen) were treated with tocilizumab. Treatment normalised temperatures within 48 hours and was associated with a significant fall in CRP from 311 (138-332) (median, IQR mg/L) to 110 (58-184) (p = 0·001). For the group, oxygen requirements fell by 60±32% (95% CI 38-81) over 1 week (p<0·001). Two of seven patients on intensive care died, five have been extubated and two discharged. All four ward patients have also been discharged.Interpretation: Following tocilizumab treatment, we observed improvement in clinical and laboratory abnormalities in this small series. Compassionate use of tocilizumab can provide valuable information to support clinical trials in patients with severe COVID-19.

General Intensive Care Unit, St George’s Hospital, London, United Kingdom *See also p. e270. Dr. Ball received funding from Aerogen and Haemonetics.

Objective To undertake a case review of deaths in a 6-week period during the COVID-19 pandemic commencing with the first death in the hospital from COVID-19 on 12th of March 2020 and contrast this with the same period in 2019. Setting A large London teaching hospital. Participants Three groups were compared: group 1—COVID-19-associated deaths in the 6-week period (n=243), group 2—non-COVID deaths in the same period (n=136) and group 3—all deaths in a comparison period of the same 6 weeks in 2019 (n=194). Primary and secondary outcome measures This was a descriptive analysis of death case series review and as such no primary or secondary outcomes were pre-stipulated. Results Deaths in patients from the Black, Asian and minority ethnic (BAME) communities in the pandemic period significantly increased both in the COVID-19 group (OR=2.43, 95% CI=1.60–3.68, p<0.001) and the non-COVID group (OR=1.76, 95% CI=1.09–2.83, p=0.02) during this time period and the increase was independent of differences in comorbidities, sex, age or deprivation. While the absolute number of deaths increased in 2020 compared with 2019, across all three groups the distribution of deaths by age was very similar. Our analyses confirm major risk factors for COVID-19 mortality including male sex, diabetes, having multiple comorbidities and background from the BAME communities. Conclusions There was no evidence of COVID-19 deaths occurring disproportionately in the elderly compared with non-COVID deaths in this period in 2020 and 2019. Deaths in the BAME communities were over-represented in both COVID-19 and non-COVID groups, highlighting the need for detailed research in order to fully understand the influence of ethnicity on susceptibility to illness, mortality and health-seeking behaviour during the pandemic.

A proportion of patients with progressive COVID-19 display a cytokine release syndrome (CRS)-like pattern of hyperinflammation and immune dysregulation in association with respiratory failure. CRS is a form of systemic inflammatory response syndrome characterised by fever, systemic inflammation, multi-organ failure, and high mortality. In severe COVID-19, there appears to be a unique pattern of hyperinflammatory responses and immune dysregulation, driven by overproduction of pro-inflammatory cytokines. In particular, very high levels of interleukin-6 (IL-6) production are associated with low HLA-DR expression and profound lymphopenia. This has fuelled intense interest in the role of IL-6 and other cytokine receptor blockade in COVID-19, using immunomodulatory treatments licensed for conditions such as rheumatoid arthritis and cytokine release syndrome (CRS). Xu reported a case series of 21 patients treated with intravenous tocilizumab 4–8 mg/kg with lopinavir/ritonavir, interferon-α and/or glucocorticoids. There was a rapid clinical improvement, and all patients were eventually discharged at an average of 15.1 days after tocilizumab. Although only two of 21 patients were mechanically ventilated, this series triggered initiation of clinical trials to test IL-6 receptor blockade in severe and critical COVID-19. Preliminary results from trials of tocilizumab and sarilumab (press release) are conflicting. In a phase 2 trial of sarilumab 200 mg, 400 mg, or placebo in 457 patients, a positive trend for clinical improvement was seen only in patients classed as critical (requiring high flow oxygen, non-invasive or mechanical ventilation) with a negative trend in patients with milder disease and no overall treatment benefit in a pooled analysis. In contrast, in a French open-label study of 129 non-ICU patients with moderate to severe pneumonia, tocilizumab 8 mg/kg reduced need for ventilation and death by day 14. We note that inclusion criteria for both trials did not include markers of hyperinflammation and outcome measures selected were inconsistent. In March 2020, we considered the compassionate use of tocilizumab in selected patients, recognising the high COVID-19 mortality and that clinical trials take time to set up and may not report in time to save patients' lives. Treatment criteria were established, which on the basis of the current literature and multidisciplinary discussion, we felt predicted the best outcomes and adhered to WHO guidelines. Criteria for hyperinflammation were based on emerging data in COVID-19 and an extrapolation of the CRS treatment indications in CAR-T therapy. Patients needed at least three of D-dimer above upper limit of normal (ULN), rising CRP, ferritin >1000 ng/ml, lactate dehydrogenase (LDH) > ULN, in addition to confirmed SARS-CoV-2, radiographic evidence of pneumonia and increasing oxygen requirement. Patients intubated and ventilated for more than 24 h (or 48 h for external referrals) were excluded as we considered that the treatment indication might have passed. Standard tocilizumab contraindications applied in addition to evidence of multi-organ failure, bacterial sepsis, and intubation for reasons other than COVID-19. Oral consent for off label prescription of tocilizumab was obtained from patients or representative, whenever possible. Seventeen patients were considered for treatment, and 11 patients (seven ventilated and four receiving high flow oxygen) received 1–2 doses of tocilizumab 8 mg/kg 11.7 ± 4.3 days after first symptoms and 2.8 ± 2.3 days after hospital admission. Over 48 h after first dose, CRP (half-life 19 h) fell from 311 (138–332) (median, IQR mg/L) to 110 (58–184) P = 0.001 (Figure 1A) and temperatures normalised (Figure 1B). Other hyperinflammation markers are as follows: ferritin (long half-life) fell by 44% of baseline over 7 days, LDH was unresponsive to tocilizumab, and D-dimers increased. For the whole group, oxygen requirements fell by 60 ± 32% [95% CI 38 to 81] over 1 week, P < 0.001. Individual parameters are shown in Figure 1C, D. The clinical course of patients from day 1 to discharge or death is shown in Figure 1E. Nine of the 11 patients were discharged at 14 ± 6 days after treatment. Four patients (A, F, J, and L in Figure 1) were given the second dose as they were judged not to have responded. Two of these intensive care patients (F and J) died from multiorgan failure, ventilator-associated pneumonia (Klebsiella aerogenes in sputum), and refractory respiratory failure. The good clinical response in this small series suggests that patients might best be selected for IL-6 blockade on the basis of the clinical manifestation of a specific pathophysiology, namely, hyperinflammation, rather than by respiratory parameters. Our cohort had higher baseline CRP values compared to those reported by Xu et al. (mean 311 versus 65 mg/L) and more patients requiring ventilation (64% versus 10%), yet had similarly good outcomes. Similarly, the French study did not include any patients who required ventilation at baseline. The responders (82%) in our series may have been in a phase of the disease driven mainly by IL-6-mediated inflammation before the development of a more complex, multi-cytokine dysregulated state due to advanced COVID-19 and/or complicating bacterial sepsis. We did not measure IL-6 levels as this was an urgent compassionate access programme rather than an exploratory clinical trial, but we recognise the potential future use of this in patient selection. For clinical trials of new treatments to have the best chance of demonstrating a significant effect, selection of appropriate population Received: 12 May 2020 Revised: 12 June 2020 Accepted: 15 June 2020

In the recent systematic review and meta-analysis by Lansbury et al. only 7% of hospitalised patients with COVID-19 were reported as having evidence of bacterial co-infection, yet >90% received empirical antibiotics1. This finding, which has been replicated elsewhere2, is hardly surprising given the challenges associated with distinguishing bacterial from viral pneumonia and that bacterial coinfection is likely to worsen an already poor prognosis in these patients3. Whilst the role of biomarkers such as procalcitonin is being explored, a desire to treat what is treatable is understandable but represents a threat to antibiotic stewardship4,5.

Copyright © 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved. 1154 www.ccmjournal.org August 2019 • Volume 47 • Number 8 Solid organ transplantation (SOT) is, in every regard, a remarkable success story. However, the single factor that limits this therapy is the supply of transplantable organs (1). The majority of organs are retrieved from brain-dead donors; although for many positive reasons, this pool is shrinking. A growing proportion of organs are being retrieved from donors following circulatory death, almost universally in the context of the active withdrawal of organ-supportive therapies. This donor pool presents a number of clinical, ethical, and societal challenges. Live donation makes up a third pool, who also present a variety of specific challenges. Most countries have freely interrogatable registries that provide illuminating data (e.g., for the United States, see https://optn.transplant.hrsa.gov/data/ view-data-reports/national-data/; for the United Kingdom, see https://www.organdonation.nhs.uk/helping-you-to-decide/ about-organ-donation/statistics-about-organ-donation/). For a contemporary comparative review of national performance in SOT, see the study by Weiss et al (2). Although we await the long-heralded and keenly anticipated technological breakthrough(s) in any or all of xenotransplantation, stem cell therapy, or biological 3D printing, bridging the supply-demand imbalance in SOT requires a two pronged approach. First, proactive, primary and secondary prevention programs that reduce the rate of growth in the population in need. Second, we need to maximize the use of the potential donor pools we have (3). This second prong can be considered as a multicomponent challenge illustrated in Figure 1. No item in this figure should be neglected, and the law of marginal gains undoubtedly applies. As a specialty, critical care medicine is central to the SOT process and has a proven track record of successful improvement programs in analogous complex clinical scenarios such as cardiac arrest management and the concept of the chain of survival. In this issue of Critical Care Medicine, Mendez et al (5) publish a retrospective, observational study into the effects of a bundle of care introduced in 2005, in brain-dead organ donors, across a single regional network in the United States. In 2008, in addition to their fairly standard package of care, the authors introduced a 360° rotational positioning protocol. By comparison with their 2005–2007 cohort of donors, the authors assessed the impact of this positioning intervention on the physiology of donor lungs, the proportion of lungs transplanted, and early graft function. By looking at their data in the successive 3-year periods up to 2017, the authors found an immediate association between their positioning protocol and improvements in both donor lung physiology and early graft function. Over the following 6 years, these improvements persisted, but in addition, in the most recent 3-year epoch, there has been a significant increase in the proportion of lungs donated. So, on the basis of this study, should we adopt this rotational positioning strategy in all brain-dead potential lung donors? The short answer is that doing so would probably result in no harm and might do some good, but the effect size cannot reliably be estimated. The intervention has physiological plausibility, is essentially cost-free, and with the increasingly common practice of prone positioning in moderate-to-severe acute respiratory distress syndrome, can reasonably be considered safe and familiar. However, during the time period of this study, many of the discreet items listed in Figure 1 have also changed. Of these, there are two particularly striking parallel changes reported by Mendez et al (5). First, there has been an international, progressive, and ongoing expansion in donor lung acceptability criteria (6) (e.g., older donors and/or those with a higher cumulative smoking history). Second, the significantly increased duration of the entire process but especially of the incorporeal donor organ conditioning phase (the time between confirmation of brain death and organ retrieval), during which marginal organ physiology can be improved to exceed the physiological threshold values for retrieval. Indeed, it is notable that this regional organ procurement organization has “no set limit on donor management times; donors are managed as long as organ function continues to improve.” This is a critical paradigm shift. It is well recognized that in the period before and for 12–24 hours post brain death, the physiological performance of transplantable organs, particularly the heart and lungs, deteriorates but that this is often reversible if optimal supportive care is provided for an extended period of 2–3 days. The pathophysiology of this phenomenon is well described. As a consequence, detailed organ donor management guidelines have become very widely adopted (7–10) and have significantly increased the number and function of organs donated (11–13). It is notable, however, that the majority of recommendations in these guidelines have been extrapolated from either the general critical care medicine evidence base or based on biological plausibility, with very few having been subjected to clinical trials in the brain-dead, potential donor population. Thus, there remain many uncertainties including (but not limited to): General considerations ● The duration of incorporeal individual organ and global optimization *See also p. 1058.

This review aims to assess the value of thromboelastography (TEG) on the general ICU, which has not been previously demonstrated. TEG is a near-patient assessment of whole blood coagulation and fibrinolysis, which reduces transfusion requirements during cardiothoracic surgery and liver transplantation.

This aim of this analysis is to explore the use of thromboelastography (TEG) in the management of hypercoagulation in the ICU. TEG allows the assessment of whole blood coagulation and fibrinolysis and hence can identify patients who are hypercoagulable.

The aim of this analysis is to explore and evaluate the role of thromboelastography (TEG) in aiding the management of patients admitted with haemorrhage to the ICU. TEG has been shown to rationalise and reduce transfusion requirements [1] but the precise role of TEG in the assessment and management of haemostasis in the bleeding patient is uncertain and has not been previously demonstrated.

Evolution has meant that our prefrontal lobes are too small, our adrenal glands are too big, and our reproductive organs apparently designed by committee; a recipe which, alone or in combination, is very certain to lead to some unhappiness and disorder. Perhaps the first recognition of a relationship between common metabolic and cardiovascular diseases dates back to 1923 1. From the early 1970s onwards, there has been widespread recognition of an association between: obesity (central/abdominal more than general 2, 3); insulin resistance (impaired fasting glucose and impaired glucose tolerance escalating onto type-2 diabetes mellitus); dyslipidaemia (raised triglycerides, lowered high-density lipoprotein cholesterol, reduced low density lipoprotein particle diameter and increased post-prandial lipaemia); and hypertension. This association was given the status of a syndrome called, amongst many things, 'the metabolic syndrome', 'the multiple metabolic syndrome', 'the insulin resistance syndrome' and 'syndrome X'. The purpose of diagnosing this syndrome in an individual was to raise awareness of the increased but potentially modifiable risks of cardiovascular disease. However, despite more than thirty years of enthusiasm for this clinical entity, the question has recently been asked by many, including one of the early promoters 4: is it still a useful concept? Further complexity is exemplified by the apparently contradictory effects of a number of the principal mediators such as uric acid 9 and ghrelin 10. Whilst debate over the definition and usefulness of the term 'metabolic syndrome' has occupied some, an increasing recognition of the worldwide 'pandemic' of over-nutrition and under-activity, which is the basis of the metabolic syndrome, has stimulated dramatic advances in our understanding of the consequential cellular and tissue pathophysiology. The industrialisation of food production and distribution has led to excess calorie intake in the majority, though shamefully, under-nutrition and even starvation remain prevalent amongst the most vulnerable in all societies. At the same time, lifestyles have become more sedentary. Biological systems adapt through evolutionary processes to changing environmental conditions, favouring mutations that enhance reproduction. As a species, we evolved in conditions of relative caloric (and sodium) restriction and with the necessity of significant daily physical activity. As a consequence, we have extensive and effective responses to caloric restriction and high intensity, physical activity, but lack any adaptive physiological (negative feedback) or behavioural responses to the opposite set of conditions 11. It appears that frequent and recurrent caloric excess results in a pro-inflammatory state 12, dyslipidaemia 13, and insulin 14 and leptin 15 resistance. At a cellular level, chronic excess energy supply damages mitochondrial dynamics, resulting in the accumulation of dysfunctional units and increases in reactive oxygen species generation 16. At an organism level, these phenomena impair appetite control 17 such that we continue to seek food despite first, not needing it, and second, its harmful effects 11. In addition, chronic caloric excess results in neuro-inflammation, which causes central dysregulation of metabolic homeostasis 18. We are designed to store excess calories as adipose tissue and thus, with frequent and recurrent exposure, we become obese. Adipose tissue has emerged as the driver of the pro-inflammatory state and the multiple endocrinopathies 19, 20 that result in end-organ damage. Both what we eat (in particular, saturated fats, sucrose, fructose and high fructose corn syrup 21) and our intestinal microbiome (reduced microbiological diversity, reduced levels of bacteroidetes and a high ratio of firmucutes to bacteroidetes 22) appear to play a role, but frequent and recurrent calorie intake in excess of need seems to be the primary driver. In addition, there is some evidence that environmental pollution from industrial chemicals, especially agro-chemicals, may be a significant co-factor 23. Furthermore, epigenetic factors, principally acquired during fetal development (and hence a reflection of maternal health), may both predispose individuals and potentially create inheritable traits in later generations 24, 25. Excess sodium intake is commonly associated with over-nutrition. Together with increased renal sodium retention and induction of sympathetic over-activity 8, this results in a high co-prevalence of hypertension. The organ/tissue-specific sequelae of these pathophysiological processes are not limited to the cardiovascular system and are briefly detailed in Table 1. Quantitative and qualitative loss of skeletal muscle ('sarcopenic obesity') 36. Osteoarthritis (lumbar spine, hips, knees 37) and gout 38 We are already seeing an increase in bariatric/metabolic surgery. Data from patients who have undergone various types of bariatric surgery and increasing knowledge of the relative importance of caloric intake and the 'enteroendocrine' system challenge the simplistic definitions of metabolic syndrome. The relationship between obesity and type-2 diabetes is becoming clearer. Obese patients undergoing profound caloric restriction 42 and bariatric surgery 43 rapidly normalise plasma glucose concentrations, and in both groups this is sustained, effectively reversing type-2 diabetes. Whilst surgical treatment offers the best chance of sustained weight loss, it is not clear how much contribution to improved glycaemic control is made by alterations in foregut endocrine modulation brought about by specific surgical procedures (Roux-en-Y gastric bypass and biliopancreatic diversion, as opposed to gastric banding). The distribution of fat (in particular, ectopic fat in the liver and pancreas) appears to be an important determinant of insulin resistance and the reduction of this ectopic fat deposition may be the best predictor of remission of type-2 diabetes with weight loss 44. Pre-operative assessment of obese patients requires a thorough review of all of the possible related conditions to enable a considered decision about potentially modifiable risk factors and the timing of surgery. Perhaps, in addition to routine screening, the following should be considered: quality of blood pressure control (24-hour record); sympathetic overactivity/reduced heart rate variability (24-hour ECG); sleep disordered breathing (Epworth score); and functional respiratory system reserve (sitting and lying spirometry with pulse oximetry). Decisions should be individualised and take into account the urgency of the surgery, the willingness of the patient to adhere to lifestyle and medical interventions and the estimated risks and benefits of a proceed vs postpone strategy. Peri-operative considerations depend on the usual variables of procedure, patient and anaesthetic preferences. Detailed planning should include the management of: chronic medications; limited cardiorespiratory reserve; glycaemic control; high thromboembolic risk; acute (often on chronic) pain; and vascular access. Intra-operative ventilation with positive end-expiratory pressure optimisation and recruitment manoeuvres are generally recommended. The role of pre-emptive, rescue and actively up-titrated, chronic non-invasive ventilation in the postoperative period has a growing evidence base 45. There is an argument for creating specialist 'pre-habilitation' and enhanced recovery pathways for obese patients. Studies of this population repeatedly find increased peri-operative rates of all morbidities and, for certain procedures, also an increased mortality 46-50. In the critical care setting, obese patients have a significantly higher incidence of all acute organ dysfunctions and although there are conflicting data regarding mortality risk 51, 52, length of stay and nosocomial complication rates are significantly higher. The most obvious consequence of these data is an additional pressure to increase critical care bed capacity. An appreciation of the chronic disease burden and lack of physiological reserve that may be associated with such patients is important. In the very obese, physiological measurements, fluid therapy, pharmacokinetics/pharmacodynamics and optimising drug therapies present considerable challenges. The problem with 'metabolic syndrome' is that it both over-specifies and over-simplifies the complex effects of over-nutrition and under-activity, which result in chronic injury to all organs (not merely the cardiovascular system), impaired quality of life, premature death and a massive burden on healthcare and society as a whole. Although insulin resistance is important, the recognition of multiple adipose tissue endocrinopathies and the chronic pro-inflammatory state are of at least equal significance. Radical policy change and innovation, at both political and public health levels, are essential to develop and implement further effective primary and secondary prevention strategies for this 'pandemic'. Meanwhile, the anaesthetist and intensive care specialist must find optimal strategies and resources to manage the planned and emergency healthcare needs of these complex and increasingly prevalent patients. No external funding and no competing interests declared.

Objetivo: O trauma grave pode associar-se a ocorrência de importante choque hemorrágico e ao comprometimento da perfusão dos órgãos. Formulamos a hipótese de que o tratamento direcionado por objetivo conferiria benefícios em termos de morbidade e mortalidade, em casos graves de trauma. Métodos: Realizamos uma busca sistemática nas bases de dados MedLine, Embase e Cochrane Controlled Clinical Trials Register com relação a pacientes vítimas de trauma grave. A mortalidade foi o desfecho primário dessa revisão. Os desfechos secundários incluíram taxas de complicações, duração da permanência no hospital e na unidade de terapia intensiva, e o volume de fluidos administrados. A metanálise foi realizada utilizando o programa de computador RevMan, e os dados apresentados são as odds ratios (OR) para desfechos dicotomizados e as diferenças médias e diferenças médias padrão para desfechos contínuos. Resultados: Foram analisados quatro estudos clínicos randomizados e controlados, que incluíram 419 pacientes. O risco de mortalidade foi significantemente reduzido nos pacientes com tratamento direcionado por objetivo, em comparação ao grupo controle (OR=0,56; IC95%: 0,34-0,92). A duração da permanência na unidade de terapia intensiva (DM: 3,7 dias; IC95%: 1,06-6,5) e no hospital (DM: 3,5 dias; IC95%: 2,75-4,25) foi significantemente mais curta no grupo de pacientes do grupo tratado conforme o protocolo. Não houve diferenças nos relatos relativos a volume total de fluidos infundidos e a transfusões sanguíneas. A heterogeneidade nos relatos entre os estudos impediu uma análise quantitativa das complicações. Conclusão: Após a ocorrência de trauma grave, o uso precoce de tratamento direcionado por objetivo se associou com mortalidade mais baixa e com menos dias de permanência na unidade de terapia intensiva e no hospital. Os achados desta análise devem ser interpretados com cautela, em razão da importante heterogeneidade e do número pequeno de estudos clínicos randomizados e controlados, que foram incluídos na análise.

PURPOSE OF REVIEW:Current pressures of organ supply and demand require maximization of potential for organ donation. The donor population is older and has more significant comorbidity than in the past.Optimal management of the donor after brain death (DBD) is essential to ensure that the greatest number of organs can be transplanted per donor. Defining evidence-based drugs and techniques to assist this has never been more important.RECENT FINDINGS:Care of patients with catastrophic brain injury incorporating supportive therapy targeted at specific goals and delivered by experienced specialists provides the best donation outcomes. Such pathways represent best practice critical care applied to this population. In this context, the value of some previously recommended therapies appears questionable and warrants reassessment. Prolonged (>24 h) incorporeal organ conditioning may have significant benefits.Extracorporeal support in the resuscitation arena is emerging and, in patients who fail to respond, may yield a new source of donors.SUMMARY:Early identification of potential DBD, best practice critical care, and achieving defined treatment goals are associated with more transplantable organs. Study of a complex intervention like donor management presents significant problems of organization, ethics and consent. This situation is recognized internationally and progress is being made.

In this, the second of two articles covering specific medical emergencies, we discuss the definitions, epidemiology, pathophysiology, acute and chronic management of pulmonary embolus and acute severe asthma.

Patients with limited cardiopulmonary reserve are at risk of mortality and morbidity after major surgery. Augmentation of oxygen delivery index (DO2I) with i.v. fluids and inotropes (goal-directed therapy, GDT) has been shown to reduce postoperative mortality and morbidity in high-risk patients. Concerns regarding cardiac complications associated with fluid challenges and inotropes may prevent clinicians from performing GDT in patients who need it most. We hypothesized that GDT is not associated with an increased risk of cardiac complications in high-risk, non-cardiac surgical patients. We performed a systematic search of Medline, Embase, and CENTRAL databases for randomized controlled trials (RCTs) of GDT in high-risk surgical patients. Studies including cardiac surgery, trauma, and paediatric surgery were excluded. We reviewed the rates of all cardiac complications, arrhythmias, myocardial ischaemia, and acute pulmonary oedema. Meta-analyses were performed using RevMan software. Data are presented as odds ratios (ORs), [95% confidence intervals (CIs)], and P-values. Twenty-two RCTs including 2129 patients reported cardiac complications. GDT was associated with a reduction in total cardiovascular (CVS) complications [OR=0.54, (0.38-0.76), P=0.0005] and arrhythmias [OR=0.54, (0.35-0.85), P=0.007]. GDT was not associated with an increase in acute pulmonary oedema [OR=0.69, (0.43-1.10), P=0.12] or myocardial ischaemia [OR=0.70, (0.38-1.28), P=0.25]. Subgroup analysis revealed the benefit is most pronounced in patients receiving fluid and inotrope therapy to achieve a supranormal DO2I, with the use of minimally invasive cardiac output monitors. Treatment of high-risk surgical patients GDT is not associated with an increased risk of cardiac complications; GDT with fluids and inotropes to optimize DO2I during early GDT reduces postoperative CVS complications.

In this, the first of two article on medical emergencies, we discuss the definitions, epidemiology, pathophysiology, acute and chronic management of atrial fibrillation and acute myocardial necrosis in the peri-operative and intensive care settings.