By Dr Peter Baumgartner, Anaesthetist, West Leederville
The list of conditions that could benefit from Glucagon-like Peptide 1 Receptor Agonists (GLP-1 RA) grows.
In June the Therapeutic Goods Administration (TGA) approved Tirzepatide as the first medical treatment for obstructive sleep apnoea (OSA). It has GLP-1 and glucose-dependent insulinotropic peptide activity (GIP).
Not surprisingly OSA is improved by weight loss, as 70% of OSA patients are overweight.
The indications for GLP-1 RA include morbid obesity, glycaemic control in Type 2 Diabetes Mellitus (T2DM), reducing cardiovascular events in T2DM, and reduction of renal deterioration in T2DM with chronic kidney disease.
Inclusion criteria suggest a BMI greater than 30, or a BMI of 27 with at least one weight related condition such as hypertension, hypercholesterolaemia or T2DM, and now presumably OSA.
Glucagon was found to increase blood glucose levels and incretins were first discovered in the 1970s. GLP-1, produced in the gut, was discovered in the 1980s. It can increase insulin release and activity.
Later its role in appetite regulation, slowing gastric emptying, and in glucose regulation was shown. When researchers discovered a GLP-1 like peptide, exendin-4 in Gila monster saliva, it led to the development of exenadine being the first drug approved in 2005 by the FDA for T2DM.
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Other drugs such as liraglutide and semaglutide followed, with newer medications showing enhanced weight loss effects, eventually leading to the approval for obesity treatment.
GLP-1 receptors are found in multiple tissues including the hypothalamus and brainstem where stimulation leads to reduced food intake.
Hepatic glucose production is reduced by activation of hindbrain receptors and autonomic nervous system influences lead to a modest reduction in blood pressure and increases in heart rate. Pancreatic action results in increased insulin secretion and decreased glucagon secretion.
Several drugs are now available, mostly once weekly injectables, with oral versions recently approved. Off-label use is widespread, and patients should be asked directly if they are taking them.
Side effects are common and may improve with time and dose adjustment. Gastrointestinal effects including nausea, vomiting, stomach pain, constipation and diarrhoea, heartburn and reflux are noted, however the absence of these does not guarantee an empty stomach.
GLP-1 RA and surgery
The advice about how to manage GLP-1 RA in the preoperative period is not well known.
It could be said that the majority of GPs and surgeons are also in the dark about how best to advise patients when they are booked for a procedure under sedation or general anaesthesia.
The concern is an increased risk of regurgitation and aspiration when airway reflexes are obtunded in the presence of a stomach that does not empty in the usual way.
GLP-1 agonists slow gastric emptying and thus cause reduced hunger and calorie intake. The effect has been seen to last over four weeks, with patients noted to still have significant food and liquid residue at gastroscopy despite fasting periods of six to eight hours being observed.
Guidelines on the management of GLP-1 RA and surgery have been produced by different organisations, with concerns specific to each specialty and disagreement about the best way to manage these medications.
Many anaesthetists believe that a compromise of withholding the injection for one week has a low risk to patient management while allowing gastric emptying to improve.
The use of a pre-operative 24-hour liquid diet is recommended widely.
ANZCA has produced the following guideline relating to GLP-1RAs and GLP-1/GIPRAs in cases requiring sedation or anaesthesia including endoscopy.
“All patients should be asked about the use of GLP-1RAs and GLP-1/ GIPRAs and be involved in discussion and planning regarding aspiration risk.”
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Elective pre-procedural cessation of GLP-1RAs and GLP-1/GIPRAs is not recommended. It risks hyperglycaemia in people with diabetes and may compromise weight control in patients who are taking GLP-1RAs and GLP-1/GIPRAs for this indication.
Patients should be asked about the use of other medications and medical conditions which may exacerbate gastrointestinal symptoms and delay gastric emptying, for example bowel dysmotility, gastroparesis, and Parkinson’s disease.
Pre-procedural diet modification with 24-hour clear fluid diet, followed by standard six-hour fasting, should be recommended
Risk mitigation options should be undertaken for those who have not withheld solids for 24 hours. These include detection of residual gastric contents, prokinetic agents, modification of anaesthesia technique, or deferral of procedure.
Author competing interests – nil.
Key messages
- GLP-1 RA increases the risk of aspiration under anaesthesia and sedation
- Ask specifically if the patient is taking a GLP-1 RA. Contact your treating team for a diabetic management plan, with monitoring of glucose levels
- Withhold dose for a week and follow a liquid diet for 24 hours before procedure.
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