Airway management research: what problem are we trying to solve?

A recent issue of Anaesthesia features a systematic bibliometric review of airway management research published between 2006 and 2017 1. In this editorial, we will discuss some of the issues which the review raises and look ahead to how, and what, airway research might be conducted in the future. The starting point for the systematic review was a debate conducted within the pages of the journal over the last couple of years. This began with the publication of an editorial debating the role of human and manikin studies by Irwin and Ward 2. They felt that airway-related research was dominated by manikin-based studies as they offer the advantage of avoiding potential patient morbidity, despite the concerns about the applicability of the findings of such work to clinical practice. The editorial included suggestions for future airway management research, including some ethical recommendations, described as a ‘Consensus on Airway Research Ethics’ (CARE). These aimed to protect patients and enable researchers to determine safety standards for airway studies. The suggestions included: restricting the number of attempts at securing the airway; limiting participants to patients of ASA physical status 1 and 2; not including patients with potentially difficult airways; and only relying on experts for evaluating new airway devices or techniques 2. In a letter in response, Cook et al. felt there was a risk that the guidelines could have a negative impact on the future of airway research. They claimed that fewer than 3.5% of airway studies involved manikins, and argued that manikin research continues to have a critical role in research, for example, in exploring the role of ‘human factors’ in airway crisis management 3. They were also concerned about the suggested exclusion of patients with an ASA physical status of 3 and above, as they felt this might preclude tertiary centres from participating in research; and by the reliance on experts for evaluation, which they thought might prove counterproductive for the next generation of researchers. They concluded by stating that these proposals might result in irrelevant or inappropriate research 3. Irwin and Ward defended their proposed guidelines, emphasising they were not an all-encompassing mandatory protocol but rather a statement of intent to promote informed discussion on some of the ethical issues surrounding patient-based airway research 4. They also argued they were reinforcing the existing obligations of ethics committee requirements and therefore only providing a framework to underpin this already accepted process. The systematic review by Ahmad et al. follows on from these discussions and attempts to elucidate some of these disputes. Using standard systematic review methodology, the authors included 1505 relevant studies overall, of which 1082 studies (71.9%) were patient studies and 322 were manikin studies (21.4%) 1. They noticed a general trend towards a disproportionate increase in patient studies over manikin airway research studies. Furthermore, their results revealed that most patients studied were those without predicted difficult airways; studies also tended to involve experienced operators when patients were the subjects. Both these attributes were in line with the CARE suggestions. Across all the studies the primary outcome was success rate in 27.4% of studies and procedure time in 22.7%. Patient-reported outcomes were the primary outcome in only seven trials. The reviewers did not distinguish between airway management in ‘awake’ or anaesthetised patients. There is, within the findings of Ahmad et al., good evidence that, even before the publication of the CARE recommendations, many researchers were already acting in accordance with the principles set out within them. It is not only airway management research that poses ethical problems; training raises issues too. Consideration of Beauchamp and Childress’ four principles of medical ethics, beneficence, non-maleficence, autonomy and justice, will always underpin what we do 5. The responsibility to further medical advances which will benefit society needs to be balanced with the obligation to protect patients from harm 5. But ethical considerations can restrict advances in practice and may give misleading results. For instance, only studying patients with straightforward airways, in keeping with the CARE guidelines, showed similar success rates for videolaryngoscopes and direct laryngoscopy 6; subsequently, in patients who were more difficult to intubate, the videolaryngoscope has proved to be superior 7. However, some leeway must be allowed: a recent study exploring the morbidity of tracheal intubation without neuromuscular blockade with a McGrath videolaryngoscope was recently published in this journal. This might appear to jeopardise the ethical principle of non-maleficence, but it can be argued that it is important to gain a full picture of the device's effects, both positive and negative 8. The principle of beneficence applies when only experts at airway management are involved in airway research with new devices 5. This was contested by Cook et al. 3, and in fact it has been shown, for instance, that the most important correlation between complications associated with awake fibreoptic intubations was the number of previous procedures performed, not the grade of the operator (trainees vs. consultants) 9. The use of cadavers for airway research is also possible, in an attempt to circumnavigate some of these ethical dilemmas, but this may present other issues such as the lack of fully informed family consent. Cadavers would appear superior in the realistic representation of airway anatomy and recent evidence has shown that cadavers have a more beneficial effect on training compared with manikins for teaching fibreoptically-guided intubation 10. Is existing airway management research relevant? El-Boghdadly and colleagues point to the ‘disconnect’ between the favoured topics for research and the habits of clinical practice. They compare the prevalence of different topics and devices in airway research with practice as reflected within the 4th National Audit Project of the Royal College of Anaesthetists and Difficult Airway Society 11. The audit reported that supraglottic airway devices were used for airway management in more than half of patients, with about two-fifths undergoing tracheal intubation. Research, on the other hand, was more commonly conducted into intubation. So, there may be an opportunity to redress the scope of coverage (see below). Likewise, it was rare for studies to include adverse or patient-related outcomes, and including these may help make research more relevant. The other aspect of relevance is the use of manikins. Ahmad et al. conclude that manikin studies accounted for more than a fifth of airway management trials. This is substantially higher than the figure given by Cook et al., who claimed manikin studies accounted for < 3.5% 3; equally they feel they cannot support the claim of Irwin and Ward that manikin studies are disproportionately over-represented in airway studies 2. Whether the results from manikin studies can be considered relevant will depend on the type of study and the question it is attempting to address. All parties agree that manikin-based research continues to play a vital role, in particular, in airway crisis management where it is ethically impossible to conduct research in patients. The utilisation of manikins in this form of research is invaluable as it contributes to the understanding of human factors such as communication, team work and decision making in airway crisis and results in a proactive ‘dynamic non-event’ safety culture in clinical anaesthesia 12. It is crucial, and at present the only appropriate approach to further human factors research in airway crisis management. The benefits of the use of manikins have been further demonstrated with research into emergency front-of-neck access manikin simulation 13. In the latter setting, using high fidelity manikin-based research for ‘human factors’ approaches in airway crisis management is a point both Cook and Irwin and Ward could agree upon 2, 3. It is, of course, also entirely possible to conduct research on human participants without significant risk; for example, a recently published comparison of the neutral and ‘sniffing’ head positions for intubation with videolaryngoscopes 14 or the use of THRIVE for rapid sequence induction 15 poses little risk of additional morbidity to the patient but do produce clinically-relevant knowledge. Ahmad et al. found a lack of research with regard to the more fundamental aspects of airway management such as education, airway assessment, pre-oxygenation and bag-mask ventilation (surely the most basic and indispensable airway management skill), the last-named making up only 7% of airway management studies 1. Prediction of the difficult airway was also poorly studied, which is especially important given that attempting to predict airway management difficulty is so commonly attempted both in the research articles studied here, and in clinical practice. It is also an imprecise activity, as shown yet again by a recent comprehensive Cochrane review of the diagnostic accuracy of commonly used tests 16. The ‘difficulty of assessing difficulty’ is often glossed over by research studies, but resolving such fundamental definitional problems is the key to performing sound research. We also do not know whether the ‘difficulty’ created by commonly used manoeuvres such as the application of a cervical collar mimics the ‘real life’ difficulties encountered in patients, although we suspect that, given that there are many causes of airway difficulty, the applicability of such models must be limited. Furthermore, the review did not distinguish between airway management under general anaesthesia and ‘awake’ techniques where the airway is anaesthetised using topical local anaesthesia. Separating out airway management from general anaesthesia creates a different paradigm for approaching both routine and ‘difficult’ airways. ‘Awake’ techniques, where the patient's own breathing is maintained, offer a margin of safety and allow for a more leisurely approach 17. The risk of the two major complications of general anaesthesia, managing failed intubation and accidental awareness, both of which stem directly from the use of neuromuscular blockade, can also be lessened, as these drugs need not be given until after general anaesthesia has been induced after the airway has been secured. Mapping out past and current research into awake techniques would be a useful addition to the study's data. One other point not really brought out in the systematic review is the role of commercial interests. We would not suggest that investigators are in the pay of the manufacturers of airway devices, or that studies are biased. However, manufacturers have an interest in marketing new devices, and research and publication play their part in this. Thus, it is possible that the airway management research agenda is shaped by commercial developmental pressures as much as by clinical need. Again, this is something that could be explored further in the future. Evaluating airway devices usually shows a logical natural progression from manikin studies, to low-risk patients in elective settings which is a practice that will continue when evaluating new devices. However, there does appear to be a trend in moving away from device research into other aspects of airway management. The Difficult Airway Society has moved away from promoting research into studies comparing two (often essentially similar) devices and instead supporting research into transnasal oxygen delivery (and ‘oxygen management’ more broadly), human factors, psychology and simulation 18. The review methodology specifically excluded an assessment of the risk of bias of included studies. In purely practical terms, this is understandable given the large number of publications involved, although the authors’ stated reason is ‘heterogeneity in study designs’. However, if it had been possible it would have added a further dimension to the study, as it would have allowed an appraisal of the relationship between methodological quality and type of device, for instance. Furthermore, although randomised controlled trials predominate, the study design ‘label’ only tells part of the story. Randomised controlled trials vary widely in how much attention is paid to the key determinants of robustness: random sequence generation, allocation concealment, blinding and how missing data are handled 19. In addition, it is seldom possible to blind the people who are inserting comparator devices to which device is being used 7, so the usual ‘double blind’ convention of masking patient and doctor to interventions cannot be achieved. Similar quality assessment tools are available for observational studies, and it would have been instructive to analyse and report the risk of bias in the included material. The worst possible finding would be that a high proportion of airway management research is not only of limited applicability to practice but also scientifically dubious. This gloomy prospect is probably unlikely, however; within a recent systematic review, most of the studies were at low risk of bias for many quality domains apart from blinding singled out above 7. We look forward to a future of high-quality, ethically sound, clinically useful studies including patient relevant outcomes and adverse outcomes, addressing (if not necessarily solving) a wide range of airway management problems. The review by Ahmad et al. sets us firmly on the right track. AS is an Editor of Anaesthesia. No other competing interested declared.