New research presented at the Association of Anaesthetists Annual Meeting in Liverpool, UK (16-18 September) and published in the Association's journal Anaesthesia shows that, for patients undergoing surgical interventions and procedures under the care of an anaesthetist, the rate of a complication known as regurgitation is 11 times more likely to occur in patients taking the new class of diabetes/obesity medications glucagon-like peptide-1 receptor agonists (GLP-1 RAs) than in patients not taking those drugs – although the absolute risk of this complication remains small. The study is led by Dr Kariem El-Boghdadly, Guy's and St Thomas' NHS Foundation Trust and King's College London, UK and colleagues on behalf of the GLIMPSE Resident Research Networks and Collaborators.
The use of GLP-1 RA type drugs, including semaglutide (trade names Ozempic and Wegovy) and tirzepatide (Mounjaro), has boomed across the UK and all developed nations in the past few years, firstly in treatment for type 2 diabetes, and then obesity, and for either or both together. Many patients (more than 40% in this study) obtain their prescriptions through online pharmacies, and thus they are unlike other drugs that are most often obtained through general practitioners (GPs) or hospital prescriptions.
Patients and the general public across the UK are broadly familiar with instructions not to eat or drink for certain periods before operations that involve anaesthesia. However, one of the effects of GLP-1 RA drugs is delaying gastric emptying or slowing the rate at which food and fluid leave the stomach. Thus, there is potential for patients who are treated with these drugs before their operations to not have their stomachs empty properly during the procedure. This in turn can increase the risk of regurgitation of their stomach contents, which could potentially enter the lungs, called 'pulmonary aspiration'.
It is unclear what proportion of patients having anaesthetic care are receiving GLP-1 RAs; what strategies are used in their peri-operative management, and whether the incidence of regurgitation and pulmonary aspiration is greater in this population.
The team thus performed a national study of adults undergoing elective or emergency procedures under the care of an anaesthetist. Patients were screened for GLP-1 RA use in the 3 months before the index procedure. Routine data were collected on patient, procedure, anaesthesia and outcomes, including pulmonary aspiration and regurgitation. The primary outcome was the proportion of patients receiving GLP-1 RAs. Secondary outcomes described the pre-operative management of GLP-1 RAs; anaesthesia and airway management in patients receiving GLP-1 RAs; and the incidence of regurgitation and pulmonary aspiration.
Of 47,039 patients from 119 sites across the UK, 1348 (2.9%) reported receiving GLP-1 RAs. Peri-operative management was variable regarding drug cessation, anaesthesia and airway management. The incidence of pulmonary aspiration and/or regurgitation in the non-GLP-1 RA cohort was 57/45,691 (0.12%) and in the GLP-1 RA cohort was 19/1348 (1.41%) (with 17 regurgitation, 2 aspiration), meaning those receiving GLP-1 RA were 11 times more likely to suffer these complications in this study.
Thus overall, 1 in 36 patients undergoing anaesthesia were receiving GLP-1 RAs. Of these, more than 40% procured the medication via non-GP or specialist prescription sources, with the most common indication being for weight management. The incidence of pulmonary aspiration and/or regurgitation in people receiving GLP-1 RAs was 1 in 71, reported most commonly during waking up from anaesthesia (53% during waking up compared with 13% at the beginning of anaesthesia and 13% mid-surgery).
The results show wide variation in practice regarding the peri-operative cessation of GLP-1 RAs. Nearly a third of patients had been advised to hold their GLP-1 medication pre-operatively, with the majority of these being omitted for 8–14 days, consistent with a request to stop the drug for 1 week. This observed practice contrasts with national guidance from the Association of Anaesthetists, which recommends continuing GLP-1 RAs throughout the peri-operative period, as stopping the medicines for less than 3–4 weeks might not be long enough for the effect on the stomach to wear off. Since tirzepatide and semaglutide have an elimination half-life of 5 and 7 days, respectively, not taking these drugs for 25 and 35 days (five half-lives) would be required to effectively eliminate them from the body's system. It is unclear, however, how long these medications need to be held pre-operatively to reduce the risk of residual gastric contents.
The 7th National Audit Project (NAP7) activity survey analysis of serious complications around anaesthesia (a national UK data collection study for anaesthesia) combined pulmonary aspiration and regurgitation events and reported a rate of approximately 1 in 660. This new study, the rate of aspiration and/or regurgitation events in patients not receiving GLP-1 RAs is 1 in 802 (57 of 45,691), which is consistent with NAP7 data. Conversely, patients receiving GLP-1 RAs had an event rate of approximately 1 in 71 (19 of 1348). These differences appear to be clinically relevant and contrast with other published data.
The authors highlight that these complications in people taking GLP-1 RAs have occurred despite clinicians tending to select airway management options that may mitigate the risks of pulmonary aspiration and regurgitation. They say: "However, although our results suggest that GLP-1 RAs are associated with an 11-fold increase in the incidence of pulmonary aspiration or regurgitation, causality cannot be determined, and this association may be due to unmeasured confounding. For example, obesity and diabetes are known risk factors for pulmonary aspiration and are over-represented in people receiving GLP-1 RAs in our cohort. Furthermore, our data may underestimate the incidence of pulmonary aspiration and regurgitation in patients who were not receiving GLP-1 RAs."
Potential limitations to the study include the protocol partly making use of anaesthetists not directly involved in the study – including those screening for GLP-1 RA use in pre-operative assessment, and then either not including the information or patients not disclosing it. Clinicians may also have been reluctant to report all aspiration/regurgitation events.
The authors conclude: "1 in 36 patients undergoing anaesthesia care receive GLP-1 RAs and their peri-operative management is variable. A range of airway management techniques consistent with reducing aspiration risk were observed, and despite this, the incidence of pulmonary aspiration and/or regurgitation was 1 in 71 in patients receiving GLP-1 RAs; this occurred most commonly as the patients wake up from anaesthesia. These data are not generalisable, but highlight the importance of patients taking GLP-1 RAs to inform their anaesthetists about this, regardless of where they get them.
They add: "As for any medication, it is important for patients to disclose they are using GLP-1 RAs before any procedure requiring anaesthesia, regardless of the source of the medicines. As use of GLP-RAs is increasing, it remains good practice for anaesthetists to consider specifically asking patients if they are taking these medications before anaesthesia."
