Practice Point: Consider holding the last dose of GLP-1 receptor agonists prior to elective surgery to reduce aspiration risk.
EBM Pearl: While case reports definitely don’t prove effectiveness of an intervention, they can be an important source of early safety signals.
Clinicians who do preoperative visits are well-versed in advising patients to stop non-steroidal anti-inflammatory drugs (NSAIDs) seven days before a procedure, to stop warfarin five days before a procedure, and they have hopefully gotten the memo that there is no need to stop beta-blockers anymore. However, guidance from the American Society of Anesthesiologists (ASA) recommends holding the last dose of any GLP-1 receptor agonists (such as semaglutide) prior to elective surgery to avoid the risk of aspiration. Practically speaking, this means holding a weekly-dosed agent for one week prior to surgery and holding a daily-dosed agent one day prior to surgery.
GLP-1 agonists are well known to cause gastrointestinal upset, including nausea, vomiting, and delayed gastric emptying, especially shortly after initiation or dose increases. Even small amounts of regurgitated gastric contents can increase the risk of perioperative complications, mainly pulmonary aspiration. Older guidelines suggested there was no need to withhold these drugs, however, the new consensus-based guidance from the ASA states otherwise.
Making sense of conflicting guidance can be tough. From an EBM perspective, in addition to the evidence, there are philosophical biases and conflicts to consider. Our first question is usually whether or to what extent the group evaluated available evidence to inform their recommendations. In this case, we wondered if there was any evidence to consider at all.
We dug deeper and confirmed that the ASA’s recommendation to hold GLP-1 agonists is related to a risk of delayed gastric emptying resulting in retained stomach contents, regurgitation, or pulmonary aspiration. A recent review article described that the evidence is derived from case reports, which is an important type of literature to highlight early safety signals. However, less clear from this (low-quality) evidence is exactly how long to hold GLP-1 agonists. There is a lot of controversy over how dangerous this risk is but not a lot of high quality evidence. We are not impressed with retrospective cohort studies which fail to even ascertain if the medications have been held prior to surgery.
When it comes to preoperative management of patients taking GLP-1 agonists, an individualized approach is probably the way to go for now, with most weight given to first doing no harm (or doing the least harm). For example, it is probably advisable to hold GLP-1 agonists for patients with a recent initiation or dose increase who are more likely to be in the throes of gastrointestinal side effects. Likewise, if they have well-controlled diabetes and are on other diabetes medications that will help maintain blood glucose control, it seems smartest to stop GLP-1 agonists because the relative risk of hyperglycemia would presumably be low. But for some patients with poorly controlled diabetes, perioperative hyperglycemia may carry its own risks. Until we have better data, the decision whether to hold GLP-1 agonists or not seems to primarily come down to balancing the estimated risk of hyperglycemia of stopping them versus the risk of aspiration without stopping them. For most people, but not everyone, they should be held.
For more information, see the topic Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists for Adults With Diabetes Mellitus in DynaMed.
