Can sugammadex reverse hypnosis?

The May issue is now available online and is full of excellent content. We encourage all readers to study carefully its contents and a enjoy a break from the infodemic amongst the COVID-19 pandemic. Firstly, this new randomised controlled trial seems to suggest that rapid reversal of deep neuromuscular blockade with sugammadex is associated with a rise in the BIS value and clinical signs of awakening. Can sugammadex really lead to sudden arousal? Avidan suggests there are several possible explanations for the findings, including that avoidance of neuromuscular blocking drugs is the best way to reduce the incidence of accidental awareness during general anaesthesia. Furthermore, he offers interesting commentary on how we sometimes might draw the wrong inference from the correct observation. 

In this study of pre-hospital emergency front-of-neck airway procedures from a nationwide trauma database in Japan, the authors describe the development and validation of a predictive model (Fig. 1). They argue it may aid in the prepare for and predict such events. In the associated editorial, Flexman et al. discuss the problems facing trialists when attempting to study rare clinical events, as well as the need for consensus guidelines for the use, reporting and analytical approaches to healthcare database research

Figure 1 The predicted, observed probability and diagnostic ability in each risk group by ‘eFONA’ score. The predicted and observed probability grouped by sum of the risk score are shown in each cohort. The observed probability is the proportion of actual eFONA procedures performed. The predictions are well‐calibrated with the observations. Error bars, 95%CI.

Robot‐assisted radical prostatectomy causes considerable discomfort, mainly during the first postoperative day. This new randomised controlled trial seems to support the use of a single shot of intrathecal bupivacaine/morphine as part of the anaesthetic technique, as it was associated with increased quality of recovery (Fig. 2). Burns and Perlas discuss the use of QoR-15 to provide a standardised, validated measure of postoperative recovery. Those wishing to determine the value of new peri-operative interventions are encouraged to use it. This new Delphi project identifies a core set of standards to be the most important and useful as quality indicators for an obstetric anaesthetic service. These include: the rate of accidental dural puncture during epidural insertion; the use of guidelines for antenatal anaesthetic referral; the use of dedicated teams for elective caesarean section; whether point-of-care testing haemoglobin testing is available; and the effectiveness of epidural labour analgesia. Carvalho and Kinsella argue this is an important step towards the creation of quality indicators for obstetric anaesthesia care. That said, more patient-centred input, rational performance metrics and evaluation of the impact of such standards are required. A further obstetric anaesthesia paper is this biased-coin up-down sequential allocation trial of the effective pre-oxygenation interval. Worryingly, one in ten parturients will be inadequately pre-oxygenated after 3.6 minutes of tidal volume breathing with a standard flow rate facemask, and the use of high-flow nasal oxygen with and without a facemask was less effective.  

Figure 2 The total Quality of Recovery (QoR)‐15 scores per time‐point. The data are presented as mean with SD error bars. The percentage and absolute decrease between pre‐operative QoR‐15 and postoperative 1 were different (p = 0.019 and p = 0.013) between the intervention and control groups. There were no significant differences between absolute values between the groups. A score of 118 (dashed line) is defined as acceptable symptom state.

How efficient are your operating theatres? How are your lists scheduled and who does it? Given operating theatres across the country are about the open again for elective work, efficiency will be key to ensuring resources are used in the best possible way. This new study from Professor Pandit undertakes a comparison of ‘booking to the mean’ vs. ‘probabilistic case scheduling’, and finds that the former is an extremely poor method of scheduling lists. With this method, 88% of lists may over-run by > 30 min and 40% will cancel patients (Fig. 3). You can read more about operating theatre efficiency in this article from our joint supplement with the British Journal of Surgery

Rightly or wrongly, Impact Factor remains the most widely used performance metric against which scientific journals are judged. According to this new analysis from McHugh and Yentis, we published 115 original articles, 22 reviews, 56 editorials and 186 letters in 2016. In the following two years, these 379 articles were cited in 1506 articles. Of these, 476 (32%) were from Anaesthesia and 1030 (68%) were from elsewhere. Some might argue 32% is too high, but there is currently no consensus on what an ‘optimal’ self-citation rate should be. Too low, and the relevance or appropriateness of the journal comes into question. Too high, and there might be a suggestion of Impact Factor gaming. One possible solution is transparency, and it is the policy for all Anaesthesia editors and reviewers not to ask authors to add or remove specific references/citations to any journal, including Anaesthesia, in their final revisions.

Figure 3 Results of booking to the mean. The actual list duration is plotted against the intended list duration (from y‐axis in Fig. 1). Had booking to the mean been accurate, most points would lie on or close to the line of identity, but the majority lie above it. Hollow circles are lists that suffered a patient cancellation (for these times, the mean time of the cancelled cases is included in the actual list time).

Elsewhere we have: a review of choice of local anaesthetic for epidural caesarean sectiona PROSPECT guideline for oncological breast surgeryan observational study of the impact of fluid optimisation before induction of anaesthesia on hypotension after inductiona discussion of carbon dioxide clearance during apnoea with high-flow nasal cannula; and a survey of regional anaesthesia practice for arteriovenous fistula formation surgeryOver in Anaesthesia Reports this new paper from Ahmad reports the first awake tracheal intubation in a suspected COVID-19 patient. You can read all new articles on COVID19 that have been accepted for publication here or that have gone through the typesetting and proofing process here.

Finally, make sure you catch up with the new guidelines for the management of glucocorticoids during the peri-operative period, which currently has an Altmetric score of 348!

Stay safe.

Mike Charlesworth and Andrew Klein

Whither ethics – on triage and Nightingales

“It may seem a strange principle to enunciate as the very first requirement in a hospital that it should do the sick no harm.” 

Florence Nightingale, Notes on Nursing: What It Is, and What It Is Not.

The coronavirus disease 2019 (COVID-19) continues to define 2020. Across the world it is causing medical, financial and social distress. It is destructive both physically and psychologically. Many countries have been grappling with national lockdown and wholescale reorganisation of their healthcare systems to cope with the expected epidemic surge (or wave) of cases – the purpose of social distancing (perhaps better referred to as aiming for people to be physically distanced and socially connected) and latterly lockdown, has been to flatten the wave from a tsunami to something smaller, and the purpose of the healthcare reorganisation has been to scale up services to deal with that wave.

In the UK we have been luckier than some. In Wuhan, China the healthcare system was rapidly overwhelmed by an epidemic surge it could not have prepared for. One well-highlighted response was to build several new hospitals – at breakneck speed and to use other communal areas for stepdown-care and oxygen delivery. Outside of the hospitals the country was put into a rigorous lockdown and this reduced R0 to < 1 and controlled the epidemic in the rest of the country – at least for now. When Lombardy, Italy became the epicentre of the emerging pandemic, its healthcare system was also overrun with Northern Italy and then the whole country entering a strongly policed lockdown.

The ‘fortune’ we have had in much of the UK is both time and information to make preparations. To get our health service in the most suitable state to deal with the pandemic effects of COVID-19, major changes to all aspects of care have been implemented. All but the most urgent surgery has been stopped. Non-urgent outpatients ceased. Hospitals have been emptied in preparation. Staff have been given crash courses in use of PPE and skills that may aid the respiratory and critical care services. ‘Cross-skilling’ has entered the medical lexicon.

Despite the time for preparation and the enormous efforts on all levels to be ready, the UK NHS has, in some parts, struggled. Hospitals have been overwhelmed by the scale of admissions, leading one to put out a desperate call for volunteer assistance to transfer critically ill patients to other hospitals when the scale of its influx was too high. In another incident, hospital oxygen supplies failed, again requiring urgent transfer of critically ill patients to other hospitals. Behind these front-page stories there are likely many more hospitals operating at or beyond their limits – even after increasing their capacity as much as they can. 

So why the title of this blog? At first glance the topics seem unrelated; but some thought reveals that triage and the new Nightingale hospitals, rapidly commissioned and brought into service across the UK, are two sides of the same coin – or perhaps two solutions to the same problem.

The models have predicted that, despite best preparations within and outside hospitals, the service will be stretched or overwhelmed in most parts of the country for a sustained period of time. That the surge of patients needing admission, oxygen and ICU care may all be several-fold too high for even the maximum capacity. There are, broadly speaking, two potential solutions: triage and Nightingales. 

Triage

Triage is a term borrowed from the battlefields of war and usually involves attempting to select, in a mass casualty situation, those patients who are most in need of immediate medical care in order to survive. The walking wounded and those unlikely to be saved are not prioritised. In the pandemic situation the process may be turned on its head (so called reverse triage) and, in the setting of inadequate resource, selection seeks to identify those patients unlikely to survive. These patients are then not offered advanced treatment but must be cared for differently, treating them symptomatically and compassionately in anticipation of their death. 

A central tenet of any medical care is that it should provide benefit and be consistent with what the patient would want. It should only be for those who can survive and only for those for whom it offers a future with a quality of life they would want. The treatment itself should not cause suffering that the patient would find intolerable. Where possible, the question of benefit is grounded in clear knowledge of what will happen to that patient, but in truth clinicians are not great predictors of outcome and so we often err on the side of caution and offer trials of treatment, including ICU care in the hope it will work. In normal circumstances the ethics of patient care is straightforward, even if predictions of outcomes and decisions are not. The ethical framework of medical care – beneficence, non-maleficence, justice and autonomy – means that the basics of decision-making around critical care (both starting and stopping it) are entirely focused on the individual. In some countries, ‘community’ is also considered a part of the ethical framework – what is right for society.

For COVID-19 in particular, we lack clear predictors of good or poor outcome, relying instead on univariate predictors of mortality such as age, high blood pressure and cardiac disease which may in reality all co-exist. We also may not have the luxury of offering trials of intensive care treatment. For it must be remembered that when COVID-19 causes critical illness, it kills most patients. Studies of those requiring ICU care, and particularly ventilation, from China, Italy and the US have all reported mortality rates of half to two thirds of patients. In the UK outcomes are the same, suggesting this illness is twice as deadly as other viral pneumonias. The myth that those dying are old and dependent is slowly being dismantled as we realise what a truly awful disease this is. Perhaps the cruellest element of the illness is that patients admitted to ICU will receive no visitors, and although who die there will not die alone, they will be surrounded only by caring staff, rather than family. 

If the number of COVID-19 cases is such that capacity is overwhelmed the prospect of triage is a real one. And this is a completely new ethical arena. It may be necessary to choose for instance between two or more patients needing one ICU bed or one ventilator, or to decide whether to stop ventilating one patient in order to offer it to a patient who is more likely to survive. These are extraordinary concepts for extraordinary times. The ethics of decision-making changes to what some describe as societal or public health decisions. Those who have argued that ‘doctors make these decisions all the time’ are wrong. Although we wrestle with decisions every day about what is right for our patient, balancing burden against benefit, this decision is about an individual. But when triage occurs the decisions are about what is in the ‘greater good’, ‘doing the best for the most’ and ‘the best for society’. This is not normal decision making but something quite alien, and which even the GMC states in normal times must not happen

In this setting doctors need help because the wider ethical environment must be considered, and the choice is—put simply—too important to be made just by doctors. Decisions about how we choose between members of society require a discussion about what society wants and will accept. A framework is needed (not a checklist) which will enable doctors to step away from the bedside, pause, consider and reach a decision which 100 days ago none of us would ever have considered. Numerous documents have been published in the last months that consider these issues – some in journals and some by learned bodies. Several are vague and opaque and some wise and helpful, particularly that from the BMA. Some of the ethical factors are shown below. It is worth pausing and contemplating these. But these frameworks need operationalising – turning conceptual and discursive documents into SOPs that real clinicians use make real decisions for real patents.

Figure 1. Some key ethical considerations for COVID-19. *Examples include healthcare workers, vaccinologists, farmers or politicians.

These are complex matters and the decisions are high-consequence. In a truly open and honest society, government or the central NHS would be providing national guidance, drawn up by our medical, philosophical and political leaders, and the National Health Service. However, that is not the case and the result is a vacuum which is being filled by necessity. The decision of how to turn principles into actions is delegated to regional networks or individual hospitals. The result is that guidelines may be drawn up by too small a group, of critical care clinicians alone, or a wider pool of doctors perhaps supported by hospital management. These guidelines may not account for the shift of focus from individual to society or factor in ethical challenges, resulting in blunt tools to score them with. With poor guidance, there is cloistered thinking and with it, the potential for moral, ethical and legal jeopardy. 

The possibility of having insufficient resources to care for all, and how that is managed has, with a few notable exceptions, not been well-grasped. But when there is inadequate resource those decisions must and will be made. Much work has been done by general practitioners and other outside hospitals to prepare the frail and ill. To advise them that hospital care may not be the right journey for them if severe COVID-19 affects them. To enable family discussions and decisions and to put alternative pathways in place, perhaps to stay at home if illness strikes. There is no doubt that this has saved many from a death alone, perhaps in distress, in hospital. This is something to be welcomed. 

Nightingales

An alternative to accepting that we have insufficient resource and planning for triage is to expand the resource to meet the demand. In the first weeks of the epidemic this effort focussed on ICU capacity – and specifically on ventilators (though now kidney machines may in fact be the greater problem). Hospitals were encouraged to expand ICUs internally up to sevenfold. The NHS ventilator challenge was established. But as well as ventilators, critical care requires (amongst many other things) space and staff. Expansion requires somewhere to else work and a bigger workforce. This was acknowledged with the GMC and other bodies writing to all doctors about the need to work in unfamiliar settings and a loosening of regulatory governance as a consequence. NHS workforce planning proposed a major change from normal standards of care (one trained ICU nurse at the bed of every ventilated patient and one intensive care consultant for each group of eight) to something quite different. In the revised guidelines, each ICU-trained nurse might have responsibility for six ventilated patients and each critical care consultant for 60. While tiers of support are layered below, this is provided by nurses and doctors who are either less experienced or whose training is from other areas of practice. It is hard to imagine that this will not have an impact on quality of care delivered – these are truly extreme measures.

The Nightingale hospitals are a proposed solution. Rather than making ICUs out of repurposed wards, operating theatres and recovery units staffed by theatre staff, it is possible to create purpose built (or at least purposefully redesigned) mega-ICUs on a warehouse scale. These are the Nightingale hospitals, first in the Excel conference centre in London and now planned in a host of settings in the UK including Birmingham, Manchester, Harrogate and Bristol. The Excel Nightingale hospital has the capacity for 4000 ventilated beds  – this alone is far in excess of all the ICU beds in the UK before the current epidemic – and the other Nightingale hospitals are each designed to care for many hundreds of patients. The vast majority of these hospitals planned to admit only patients needing ventilation. Scale can provide efficiency and workforce planning breaks down the normal bedside delivery of ICU care into an almost bewildering list of teams – one each for airway, lines, nutrition, turning, comfort etc. At first sight this is a perfect solution to the capacity problem – physically expand the system to the extent that the capacity is sufficient, and the problem is solved. Hospitals will have their space back and may be able to start to recommence services they have had to mothball. Perhaps a semblance of normality can return to NHS services. 

However, this solution has its own challenges. The Nightingale hospitals solve only one of the main challenges to ICU expansion: space. ‘Stuff’ (equipment) and staff remain constrained. The Nightingale hospitals will necessarily be staffed by the same skilled staff who would otherwise be working in the hospitals they serve. And these staff will no longer be available there. As the Nightingale hospitals are set up on a regional basis this may mean either staff commuting long distances or relocating for a period. These staff will be working in a new environment in new teams and both changes will require training and adaptation. The same is true for equipment – if a ventilator or renal replacement machine is sent to a Nightingale hospital it cannot be used at a local hospital. So, it should be clear the Nightingale hospitals whose scale may be beneficial in providing economies of effort, are using staff and equipment that would otherwise be at the hospitals they serve. They are not so much additional capacity as relocated capacity. In order for patients to be treated at the Nightingale hospitals patents must be transported there – another service requiring significant redeployment of staff and equipment. The Nightingale hospitals are a bold and ambitious attempt to solve an extraordinary problem. Judging if, when and how to use them will be the challenge. The already stretched service will undoubtedly be further stretched by deployment of the Nightingale hospitals.

Hope

As always, we finish with a message of hope. If the surge of cases becomes too much for our NHS, either the Nightingale hospitals or triage may provide the necessary solution to the problem. And it is essential that we are prepared. Far better would be that neither are needed. Across the world, the impact of lockdown is being felt psychologically and financially – but it is working. It worked in China, it is working in Italy and Spain. It is starting to work in the UK. There is evidence that the rate of new cases is falling and the epidemic curve is flattening – with correlation between a region’s compliance with lockdown and the local flattening of the curve. Although the death rate is distressingly high there is evidence that the rate of new cases is falling. As deaths lag new cases by several weeks, it will take some time for this change to be seen. In a week or ten days a reduction in new infections will translate into a fall in hospital admissions, then to a reduction in ICU bed requirement and in a few weeks to a fall in deaths. Projections are changing rapidly but the evidence is mounting that the national effort — by the government, the NHS and the whole population— is working. If we are lucky, both triage and the Nightingale hospitals will become important academic projects but neither needed to be put fully into action. 

Tim Cook and Kariem El-Boghdadly

The (invisible) consequences of COVID-19

The global impact of the novel coronavirus 2019 (2019-nCoV) pandemic has been massive. Schools have been closed. Elite and recreational sport has been stopped. Conferences, medical and otherwise have been delayed or cancelled (including a coronavirus conference). Countries have closed their borders. Global economies have all but collapsed. This pandemic has left its mark on China and is now settling in the current epicentre: Europe, though this is likely transient, and it may soon move to America. Today the number of confirmed cases has passed 1 million.

The ever-changing numbers 

Epidemiological patterns that have previously been described in China are replicable in many other countries. This follows what is called exponential growth. This means that the number of new cases increases by a given factor every day (Fig. 1). In most countries, the first 100 confirmed cases of corona virus disease 2019 (COVID-19) are often sporadic and take some time to spread to large numbers of individuals. However, once the first 100 cases are confirmed in each country, the subsequent growth is remarkably predictable (Fig. 2). For example, the time it takes a country to get from 100 to 1000 confirmed cases is fairly consistently between 6–9 days. The next 1000 cases occur in the subsequent 3–4 days. By 14 days, most countries can expect to have had their first 6000 patients with COVID-19. 

Figure 1
Figure 2

In Italy and Iran, the exponential growth continued, and each reached more than 12,000 cases exactly 17 days after they hit 100. Today, the numbers in Italy and the USA are higher than those reported from China. However, the South Koreans managed to slow their spread much earlier than the Italians for example by implementing aggressive testing and isolation measures, a highly effective public information and social isolation campaign, early treatment of those that require it, and rigorous decontamination policies. This provides an opportunity for other nations to strongly consider some of these effective (albeit obvious) measures to be implemented early. The intermediate and longer-term impact of these policies are unclear.

The attack rate (the proportion of the population that will be affected by the virus), is likely to be anywhere between 30-80% of individuals. Thus, the importance of effective public health measures is less about limiting the total number of affected individuals, but more about spreading that number over a longer period of time to enable the health service to cope with the demands. Put another way, if a restaurant has capacity for 25 people and 100 people turn up for dinner on one night, the restaurant will be unable to accommodate them physically or with food. If those same 100 individuals attend over four days or more, the restaurant may still be busy, but still able to cope. 

Variations in mortality

The case fatality rate (number of deaths/number of confirmed cases) continues to rise. Whilst in China, this rate is approximately 3.9%, in Italy it is just above 10%, and this figure will only increase. Mortality is age-sensitive, and the Italian population is on average older than that of China. Latest analyses suggests that the global case fatality rate may be closer to 5.4%, and the infection fatality rate (number of deaths/number of infections) could be as high as 0.9%. The daily increase in deaths per capita is also an important consideration, with both Spain and the UK showing worse trajectories than Italy and the USA (Table 1).

As devastating as these figures might be, they only tell one part of the story.

All of the victims

Beyond the number of individuals who contract COVID-19 and those that succumb to it, there is a population of people who become critically ill with it. It is estimated that 1.5% of all infected patients need to be admitted to the intensive care unit (ICU), which could be somewhere in the hundreds of thousands in the UK. 

Accepting that non-clinicians may be reading this: being admitted to the ICU is a traumatic experience. It  often involves being anaesthetised and placing a tracheal tube with ventilation delivered by an increasingly scarce resource. Cannulas and catheters are placed into arteries and veins, the nose, and the bladder.  Patients are given analgesia, vasopressors, antibiotics, fluids, neuromuscular blocking drugs and various other drugs. They are unable to move for themselves so must be turned regularly, including being nursed in the prone position for much of the time. If there is evidence of renal failure, their blood must be filtered with another limited resource: haemofilters. In their unconscious state they are unable to communicate with their families, but because of the contagious nature of the virus, no visitors are allowed anyway. This resource-intensive treatment is often initiated very quickly, but in patients with COVID-19, generally lasts for approximately 10 days. Some patients, particularly young patients who do not respond to treatment immediately, may remain in ICU for far longer. Around half of patients will survive their stay in ICU. For these the road to recovery is long. Patients will be weak, may have ongoing respiratory problems, and perhaps most importantly, the long-term psychosocial impact could be traumatic. 

Even during an epidemic, the patients with COVID-19 are only part of the responsibilities the health service has. Whilst the resources invested in COVID-19 are already, and will continue to be unprecedented, there is no doubt there will be a major impact on other services that each form part of an effective healthcare system: cancer treatment; cardiac surgery; orthopaedic surgery; psychiatric services; and much more. As resources are stretched to breaking point, those patients who would normally have received prompt and effective treatment may have this care delayed to the detriment of their short- or long-term health. The idea of a waiting list is effectively gone, and patients previously waiting for care could see that wait prolonged to the point of being suspended in an uncertain limbo. The health of some of these patients will deteriorate: they may have pain they might otherwise not have had. Some will die earlier than otherwise. The national mortality rate from disease unrelated to COVID-19 will increase for some time to come. 

The impact on healthcare workers cannot be underestimated. Frontline staff who place themselves in direct contact with patients with COVID-19 are at a greater risk of acquiring the disease. In Italy, nearly 1 in 10 new diagnoses have been in healthcare workers. Anaesthetists and intensive care physicians in particular are at high risk due to exposure to a high viral load during procedures performed close to the airway: called aerosol-generating procedures. So too are ear, nose and throat and eye surgeons, as well as dentists. The data remain unclear as to whether mortality rates are greater in healthcare workers or not, and studies are being undertaken to determine this, but it is clear that access to appropriate personal protective equipment (PPE) is of the highest priorities but the lack of access is perhaps one of the biggest threats. Moreover, there remains debate about what appropriate PPE is for different settings. Surgeons have suggested that everyone in an operating theatre setting should don full PPE for all patients, while this disagrees with other recommendations suggesting that full PPE should only be used when there is a significant risk of aerosolisation. These areas of contention leave healthcare workers confused and may compound the high levels of anxieties in healthcare workers. Healthcare workers may also be concerned about taking the infection home to their family and some are even making the decision to remain  isolated from their families in order to reduce risk.

To add to this burden, capacity and resource may simply not be enough to match demand. Frontline staff will shoulder a tremendous responsibility for difficult clinical decision-making, and ultimately in some cases for selecting who is given the best chance of survival and who cannot be saved. The NHS is currently commissioning, planning and constructing at great pace a network of Nightingale hospitals in exhibition centres and empty universities. The aim is to provide much needed additional capacity and to provide a safety valve for current hospitals. It is ambitious and to an extent a gamble to spread the resource and staff even further, but one we all hope will succeed. We will soon know.  

Hope

Despite the devastating numbers of diagnoses and deaths due to COVID-19, the reduction in R0 in China is reassuring, with the number of new cases falling dramatically and locally spread cases being almost zero. In Italy, their daily rate of new cases has plateaued at around 6000, and may have peaked. The world’s largest democracy, India, has locked down with fewer than 500 cases at that time. And the public health measures implemented in Switzerland mean that their rate of increase has also plateaued. All the evidence is that this will pass. 

In the UK, individual hospitals have spent the last few weeks preparing for the worst, and at an institutional level, preparation is probably as good as it could be given the circumstances. The availability of PPE and diagnostic testing for frontline staff is increasing. And the public have never been as well-informed about a health crisis as they currently are.

We encourage all readers to heed public health advice, healthcare professionals to continue to train and prepare for the management of patients with COVID-19, and for institutions to continue to be agile and responsive to the rapidly changing demands on healthcare resources. 

Dr Kariem El-Boghdadly and Professor Tim Cook