We thank Deng et al. for their interest in our recently published article, “Intraoperative Mechanical Power and Postoperative Pulmonary Complications in Noncardiothoracic Elective Surgery Patients: A 10-Year Retrospective Cohort Study.”  Indeed, the fraction of inspired oxygen (Fio₂) was recorded but not extracted nor analyzed. Our statistical analysis plan did not include the study of Fio₂ because we chose to use oxygen saturation measured by pulse oximetry (Spo₂) instead. In our center, the systematic intraoperative use of high Fio₂ (greater than 0.8) has never been implemented. Fio₂ at 0.5 has been the usual practice until recently, when lower values, titrated to maintain Spo₂ greater than 95%, have been in use. We therefore believed that Fio₂ information constrained in most cases to a very limited range around 0.5 would not be informative. In contrast, several studies have demonstrated the importance of intraoperative Spo₂ in the occurrence of postoperative pulmonary complications. In the study by Hino et al., the pulmonary Apgar score (which includes intraoperative Spo₂) was able to predict pulmonary complications.  More recently, Song et al. showed, in a geriatric patient population, that the occurrence of hypoxemia (indicated by low Spo₂) was predictive of postoperative hypoxemia.  Therefore, we decided to use episodes of desaturation with Spo₂ less than 96% as a more informative variable for assessing intraoperative pulmonary complications and potential confounding factors for postoperative pulmonary complications.

Glucagon-like peptide-1 (GLP-1) receptor agonists are approved for type 2 diabetes mellitus and weight loss. However, concerns have emerged regarding their potential to increase the risk of perioperative regurgitation and aspiration pneumonitis, despite standard fasting protocols.  The American Society of Anesthesiologists (ASA; Schaumburg, Illinois) published a consensus-based guideline in 2023 recommending holding GLP-1 agonists before procedures.  In contrast, the American Gastroenterology Association (AGA; Bethesda, Maryland) recommended an individualized approach regarding the use of GLP-1 agonists during the pre-endoscopic period.  These recommendations were based on observations of increased gastric content in fasting patients treated with semaglutide.^1,3  A recent cohort study reported an increased risk of aspiration pneumonia among GLP-1 agonist users undergoing endoscopic procedures. However, in this study, there appeared to be differences in the baseline characteristics between patients who received GLP-1 agonists and those who did not, raising concerns about confounding bias influencing the risk estimates.  We aimed to perform a propensity score-matched cohort study to compare the risk of aspiration pneumonia between patients who were on GLP-1 agonists within 1 month before endoscopic procedures and those who were on GLP-1 agonists more than 1 month before endoscopic procedures.

We utilized the TriNetX Analytics Network database, which includes de-identified electronic health records from greater than 101 million individuals and 70 healthcare organizations.  The study was deemed exempt by the institutional review board and followed the Strengthening the Reporting of Observational studies in Epidemiology (STROBE) guidelines.  We included adult (age 18 yr or older) patients with type 2 diabetes, body mass index (BMI) 30 kg/m² or greater, or BMI 27 kg/m² or greater with a weight-related comorbidity between April 2005 and February 2024 (Supplemental Digital Content 5, https://links.lww.com/ALN/D646). Pregnant patients were excluded because GLP-1 agonists are contraindicated in this population. Because there is a shortage of GLP-1 agonists in the United States, some patients might not have started their prescribed medication. As this was a database-driven study without direct access to the electronic health records, we were not able to determine if patients in the GLP-1 agonist cohort were actually on GLP-1 agonists. To overcome this issue, we specified that patients in the GLP-1 agonist cohort received a GLP-1 agonist prescription at least once between 1 and 12 months before the endoscopy and at least once within 1 month before the procedure. The non-GLP-1 agonist cohort included patients who were prescribed GLP-1 agonists within 12 months but not within 1 month, 3 months, or 6 months before the procedure, and those never prescribed GLP-1 agonists before the endoscopy. The index date was the endoscopy date. The primary outcome was the incidence of aspiration pneumonia within 7 days after endoscopy (Supplemental Digital Content 1, https://links.lww.com/ALN/D646). Cohorts were propensity score-matched in a 1:1 ratio using predetermined variables that included demographics, BMI, hemoglobin A1c, comorbidities, and the use of glucose-lowering and gastrointestinal agents. We estimated the association between GLP-1 agonists and outcomes by computing the relative risk using a matched pair logistic regression model on the TriNetX platform, which utilizes SAS version 9.4. We evaluated the effects of GLP-1 agonists on intubation, admission to the intensive care unit, and death within 7 days after endoscopy. We performed a sensitivity analysis evaluating the duration of GLP-1 agonists and risk of aspiration pneumonia. We also conducted subgroup analyses evaluating patients who received upper or lower GI endoscopy, had GI comorbidities, received daily or weekly GLP-1 agonists, and endoscopy with or without general anesthesia. All P-values were two-tailed and considered statistically significant if less than 0.05.

Of the 82,004 eligible patients, 29,820 (36.4%) were in the GLP-1 agonist cohort and 52,184 (63.6%) in the non-GLP-1 agonist cohort (Supplemental Digital Content 5, https://links.lww.com/ALN/D646). Patients in the GLP-1 agonists cohort had a higher baseline prevalence of morbid obesity (20.0% vs. 16.9%) and type 2 diabetes (78.4% vs. 69.2%). After propensity score matching, all covariates were well-balanced between cohorts (table 1). Mean ages were 58.5 (±10.9) and 58.4 (±11.1) years, respectively. Esophagogastroduodenoscopy and colonoscopy were performed on 48.7% and 68.7% of patients, respectively. In the logistic regression analysis, patients on a GLP-1 agonist within 1 month of endoscopy had a similar risk of aspiration pneumonia compared with patients on a GLP-1 agonist between 1 and 12 months of the endoscopy (risk ratio [RR], 1.14 [95% CI: 0.88-1.47]) (table 2). Similarly, patients on a GLP-1 agonist within 1 month of endoscopy had a similar risk of aspiration pneumonia compared with patients not on a GLP-1 agonist within 3 or 6 months or those who were never prescribed a GLP-1 agonist before the endoscopy. Similarly, in the sensitivity and subgroup analyses, the use of GLP-1 agonists was not associated with an increased risk of aspiration pneumonia or other outcomes (Supplemental Digital Content 2, 3, 4, https://links.lww.com/ALN/D646).

In this cohort study, the use of GLP-1 agonists within 1 month before endoscopy was not associated with an increased risk of aspiration pneumonia among patients with type 2 diabetes or obesity undergoing endoscopic procedures. Contrary to guideline recommendations, our results suggest that GLP-1 agonists are likely safe in the perioperative period, and whether GLP-1 agonists should be held before endoscopies should be individually assessed. Limitations of this study include the observational design, which implies that there were likely unmeasured or unmatched confounders. This was a database-driven study without direct access to medical records. Therefore, we were only able to capture the outcomes using International Classification of Diseases (ICD) codes, raising the possibility of misclassification. We were unable to obtain the doses of GLP-1 agonist treatment as the TriNetX database did not provide data on doses. It is important to note that this study only showed no increased risk of aspiration pneumonia in patients who had GLP-1 agonist treatment within 1 month before endoscopy. Of note, we were unable to confirm if patients in the GLP-1 agonist cohort were started on GLP-1 agonists due to the lack of access to electronic health records. Nevertheless, we specified that patients should have been prescribed a GLP-1 agonist at least once between 1 and 12 months before the endoscopy and at least once within 1 month before it.

In conclusion, this population-based study found no association between the use of GLP-1 agonists within 1 month before endoscopy and the risk of post-endoscopy aspiration pneumonia. Further studies are warranted to guide an individualized approach to the management of GLP-1 agonists during the pre-endoscopic period.