Evaluation of an ambulatory care pathway for patients with nitrous oxide-induced myeloneuropathy

Introduction

Nitrous oxide (N₂O) has been increasing in popularity as a recreational drug in recent years1 with 230 000 16–24 year olds in England and Wales estimated to have taken N₂O in 2021–2022.2 N₂O-induced myeloneuropathy was first reported in dentists in 19783 and followed by relatively few reports until a sharp rise in published case reports in recent years.4 Patients experience a range of neurological syndromes from peripheral neuropathy to subacute combined degeneration of the cord.5 N₂O is widely thought to cause myelopathy through the inactivation of vitamin B₁₂, preventing the formation of myelin.6 Despite many cases resulting from chronic and heavy use of N₂O, there are reports of patients with ‘one-off’ use of only several balloons.7 8 The predictors of a poor outcome and the susceptibility to sustaining neurological damage remain undetermined. Permanent disability has been reported, often in those continuing to use N₂O.9

Until recently, there was no consensus on treatment guidelines for suspected N₂O-induced myeloneuropathy. In response to a rising number of cases, a dedicated N₂O-myeloneuropathy pathway was established at the Royal London Hospital in September 2021, which formed the basis of the current national guidelines4 10 aiming to standardise investigations and treatment. Following its inception, the pathway was further optimised using quality improvement methodology in three further cycles. Briefly, cycle one established the pathway, aimed to rationalise biochemical testing, reduce hospital admissions, and increase the number of patients that had B₁₂ injections in ambulatory care rather than being referred to primary care. It included 10 patients from July 2021 to September 2021 and 13 patients from September 2021 to July 2022. Cycle two included 27 patients from August 2022 to October 2022 and aimed to increase in-hospital awareness through internal promotion of the pathway and to add recommendations to improve documentation of N₂O abstinence. Cycle three included 23 patients from December 2022 to March 2023 and aimed to establish an objective measure (a 10 m walk test) of patient function to aid treatment decisions regarding B₁₂ discontinuation. Successive audit cycles led to improvements to the pathway over time.11

Patients with N₂O-myeloneuropathy often do not attend follow-up appointments, similar to those with other substance abuse issues.12 The eventual clinical outcome of patients with N₂O-myeloneuropathy is often unavailable due to loss to follow-up.5 13–16 Whether high rates of non-attendance persist despite a structured N₂O treatment pathway is unclear. We evaluated the reasons for discharge from the ambulatory care pathway. Furthermore, whether attendance can feasibly be improved using novel methods of patient engagement is unclear.

Methods

Patients on the N₂O ambulatory care pathway at the Royal London Hospital were identified from multidisciplinary team (MDT) lists between 9 September 2022 and 25 April 2023. N₂O MDT meetings consisted of a neurology consultant, an acute medicine consultant, and an ambulatory care nurse. Clinical data were collected via Millenium PowerChart (Oracle Health), the electronic clinical records system at Barts Health National Health Service (NHS) Trust. Demographic data on age at presentation, sex, N₂O use, smoking, other drug use, alcohol use, ethnicity, religion, and indices of multiple deprivation calculated from postcode were collected. Clinical data were collected on initial presentation, including duration of symptoms and initial symptoms, number of B₁₂ injections, the number of clinical reviews, discharge outcome, and final neurological examination. On the Royal London Hospital N₂O ambulatory care pathway, patients are discharged after two consecutive non-attendances for either B₁₂ injections or clinical review, if no reason or warning was provided. Patients could re-engage with the pathway after a period of non-attendance and were restarted on treatment and had clinical reviews scheduled if necessary. B₁₂ injections were continued until the patient recovered or plateaued, according to national guidelines.4

To improve attendance and engagement of users with the Ambulatory Care treatment pathway, a 12-item questionnaire was devised with input from a consultant neurologist consisting of questions that were answerable with a numbered option or a binary yes/no response (table 1). This aimed to remind patients about their ongoing condition and the importance of treatment, with the secondary aim of gathering more granular data on the impact of treatment on a week-to-week basis. The questionnaires were sent via WhatsApp to patients who had consented, once per week, with up to three reminder messages every few days before participants were no longer contacted. The questionnaire was sent as text, that could be copied and pasted, or as a Portable Document Format (PDF) according to participant preference. WhatsApp was selected as the mode of communication as response to email and phone calls in this patient group had been noted by staff to be low, and WhatsApp has been used to successfully conduct health systems research in settings with highly mobile and difficult-to-contact participants.17 Patients from the MDT lists from 27 January to 14 March were approached to be enrolled on the weekly WhatsApp survey project. Patients who had presented to the emergency department more than 2 weeks prior were not approached, as any data collected may have missed initial improvement on commencing B₁₂ injections. Patients were approached either in ambulatory care when attending for intramuscular B₁₂ injections as part of the treatment pathway or over the phone. Patients were required to return a consent form in order to participate (online supplemental appendix 1).

WhatsApp was decided on as the most suitable mode of communication as the majority of young people already have the app installed on their phones for regular use. This allowed for two-way messaging and the app is end-to-end encrypted, meaning the data were not accessible by WhatsApp or any third parties. The consent form included advice for patients such as having a passcode lock on their phone and deleting messages after they had been received by the team to increase personal security of potentially sensitive health data. Overall, it was decided that the risk of not trying novel ways of engaging with patients with N₂O-induced myeloneuropathy outweighed the potential data protection concerns over the use of WhatsApp. SNOMED CT codes were added to the clinical records of all cases used for analysis, as requested by the Chief Clinical Information Officer. SNOMED code "2765991000000115—subacute combined degeneration of the spinal cord due to the use of N₂O" was added for any patient with confirmed or clinically probable SACD as confirmed by the MDT. SNOMED code "2765741000000111—N₂O misuse" was added to all clinical records of those confirmed to have used N₂O recreationally. Statistical tests and graph creation were performed using RStudio V.2023.03.1+446 ‘Cherry Blossom’ release for Windows.

Results

Survey participants

Of the 12 patients approached to receive weekly questionnaires via WhatsApp, 8 expressed an interest in participating and 5 returned a consent form (online supplemental appendix 1). All five participants were withdrawn due to non-response after three reminder messages (4/5) or participant choice (1/5) (figure 1).

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Figure 1

Flow chart of participants approached to participate in the survey project. The number of surveys returned, the reason for withdrawal and outcome of treatment on the N₂O ambulatory care pathway are shown. N₂O, nitrous oxide.

Discussion

Patients with N₂O-related neurological harm in this cohort had high rates of discharge due to non-attendance, despite the implementation of the dedicated ambulatory care pathway. The pathway has undergone multiple cycles of quality improvement; however, novel approaches are still needed to improve access and adherence for N₂O patients. The high rate of non-attendance is in concordance with a large multicentre case series, in which only 32% of patients had a neurological exam reported 28 days or more after initial presentation, indicating that non-attendance has been an ongoing issue since at least 2016.8 In our centre, on this pathway, 62.5% of patients being discharged for non-attendance highlights the scale of the issue faced in providing effective treatment to this population. Loss to follow-up rates have varied in small case series of 3–20 patients from 15% to 60%.5 14–16 18 There is no way of knowing if these non-attendances were due to clinical improvement, frustration at lack of apparent improvement, patient choice, or difficulty accessing healthcare in this way. Disability resulting from N₂O use or social factors such as being unable to afford public transport to attend appointments may play a role in non-attendance. Residual neurological deficit was not associated with non-attendance in this cohort, but the sample size is relatively small. Younger patients were less likely to complete their treatment course, which may indicate further issues accessing and engaging with the pathway. Patient-led initiatives, considering the self-reported needs of this group, will be essential in creating effective and lasting initiatives to improve outcomes. Although this will be challenging, given the high rate of non-attendance and oftentimes an unwillingness to stay in the department, it is necessary to continue to develop new initiatives to engage with patients and coproduce future projects. This may improve participation and help to improve healthcare for patients with N₂O-induced myeloneuropathy in the future.

The length of symptom duration prior to presentation was significantly longer in the group that was discharged for non-attendance. This may indicate a reluctance to seek help from healthcare and a similar reluctance to engage once on a treatment pathway. The high rate of non-attendance means it is difficult to effectively evaluate the impact of treatment on final outcomes. Many of the unknowns in the pathogenesis, clinical course and long-term outcomes of N₂O-induced myeloneuropathy will require collaboration with patients to determine. The predictors of both a full recovery and poorer outcomes are yet to be determined, with B₁₂ status and metabolism suspected to play a role in susceptibility to neurological sequelae.14 60% of patients had some neurological deficit remaining at their final neurological examination prior to discharge, with this percentage likely higher given many patients did not attend any clinical reviews thus their level of deficit is unknown. This high proportion, as well as sensory issues being the most common, is consistent with other findings.8 19 Accurate and consistent SNOMED coding of N₂O-induced myeloneuropathy cases is hoped to build a database of patients. In the future, this group data could help with determining predictors of outcomes and help inform future treatment guidelines.

The lack of participation in the WhatsApp survey project was disappointing but in line with wider difficulties in engaging this patient population. Given the high rates of non-attendance of patients with N₂O-induced neurology, low rates of participation in an optional survey were to be expected. There is no obvious incentive for participants to participate in a service development project such as this one. This led to a high non-response rate even among those who consented. This may reflect several aspects. N₂O users were already identified as having high rates of non-attendance for treatment and clinical reviews. Rather than representing an easier method of engaging with healthcare via a familiar method of communication, this likely represented another task that added to the existing B₁₂ injection appointments and clinical reviews. The user experience of returning surveys via WhatsApp may have contributed to the lack of engagement. The participant had to copy and paste the survey, adding their answer to each question, or write on a PDF version of the survey. In the future, using an app already optimised for patient use, such as ‘Patients Know Best’ which provides personal records to patients, may provide a more user-friendly experience. Communicating with patients via an app specifically for healthcare information and communication may improve participation, as all of their healthcare-related information and tasks would be in one place with the added benefit of increased data safety.

This project had multiple limitations, aside from the low participation. Although a potential way of tracking participants’ symptoms over time, it was difficult to establish an accurate baseline. The identification of the participants at biweekly MDTs and the time taken to gain consent meant most were contacted a minimum of a week after they first presented to the emergency department. Identification and enrolment in a study would ideally be carried out at the first presentation in future to establish an accurate baseline. With the implementation of regular MDT meetings and a dedicated clinical fellow, undertaking a similar project in future would be less susceptible to these issues. Additionally, participants could respond to messages at any time and often waited many days before returning surveys. This provided a level of uncertainty as to when in their clinical course the response correlated. Using an app in future to allow participants to enter data at a time of their choosing, with automated reminders may eliminate some of the difficulty in recording timely data. Codesigning future initiatives with patients may aid in improving participation and ultimately attendance at ambulatory care pathway appointments. Exploration of the underlying reasons for non-attendance is needed, and appropriate social care provided where necessary to address barriers to accessing healthcare.

Despite the limitations, valuable lessons were learnt from this study. It is important to continue to devise novel ideas for engaging patient groups in their care. The population that presents with N₂O-induced myeloneuropathy is generally young, less than 30 years of age, and well-versed with technology. Utilising methods of communication that patients are already familiar with and regularly use may improve engagement with healthcare services. Given the reported low attendance at appointments made via email or letter, these methods of communication were not suitable to distribute the questionnaires. The trust uses AccuRx messaging to notify patients of appointments which was considered for this project, however, this only allows for one-way messaging. WhatsApp is widely used by young people, and although not commonly used in the healthcare setting, in this case, with a population at risk of permanent disability due to disengagement with treatment, the risk of not trying a new method of communication was deemed to outweigh the risks around the use of WhatsApp to receive clinical information. Integrating an app for symptom tracking or communication with healthcare teams may be a successful step in the future. Ultimately, it is up to the individual as to whether they engage with their healthcare and the tools available to them. Hence, education is vital about the health risks of N₂O and the potentially permanent disability that can result from misuse to motivate patients to engage with their treatment.

It has been suggested that certain populations may have a higher likelihood of using N₂O, with those from Asian British backgrounds overrepresented in this cohort and others.8 Misunderstanding surrounding religious and cultural permissibility of N₂O as a drug exists in Asian communities.20 31/56 (59.6%) of patients identified their religion as Islam according to their demographic data on Millenium PowerChart. This proportion may be higher, with no data on religion for a further 17 patients. Although N₂O is not permissible in most mainstream interpretations of Islam, misunderstanding combined with the odourless, inconspicuous nature of the drug may lead to prevalence in young people from this community. Religious and youth groups are key audiences to empower with knowledge of the neurological risks of N₂O.21

More needs to be done to engage patients with N₂O-induced myeloneuropathy with the treatment pathway to improve outcomes. This is even more essential as the UK government reclassified N₂O as a Class C drug under the Misuse of Drugs Act 1971 in November 2023.22 Criminalisation risks further preventing engagement with healthcare for those with disability caused by N₂O use.23 It is essential that those with symptoms due to N₂O feel able to seek help from healthcare providers and engage fully with their treatment.

Conclusion

Patients with N₂O-related neurological symptoms had high rates of non-attendance to follow-up appointments, and the majority continued to be symptomatic at the time of last clinical contact. WhatsApp represents a communication method already commonly used by young people that may be able to be used for healthcare purposes. Despite the poor engagement with the surveys via WhatsApp, high rates of discharge for non-attendance indicate it is necessary to develop new initiatives to facilitate the engagement of patients on the N₂O ambulatory care pathway with their treatment. In the future, the co-creation of initiatives with patients would aid in developing avenues that help patients to fully attend their care and maximise recovery.