Den europeiska läkemedelsmyndigheten EMEA har fått signaler om risker med GLP1 vid anestesi. De har ett extra möte kring detta denna vecka. 

 

Sett risker med aptitdämpande läkemedel

Det handlar om aptitdämpande läkemedel av typen GLP-1-analoger som finns både som diabetesläkemedel diabetes och som behandling av fetma. Några exempel är Ozempic (semaglutid), Wegovy (semaglutid) och Mounjaro (tirzepatid).

Signalerna till myndigheten säger att sådana läkemedel misstänks ha bidragit till att patienter under narkos fått ned maginnehåll i lungorna. Detta kallas aspiration och kan även leda till lunginflammation.

 

Fasta inför operation hjälpte inte

Inför en operation där man blir sövd brukar patienten få instruktion om en viss tids fasta. Skälet är att magsäcken bör vara tom under narkosen så att maginnehåll inte kan komma upp och andas ned i lungorna.

Enligt nyhetsbyrån Reuters har medicinska tidskrifter dock på senare tid rapporterat om enstaka fall där patienter som tar GLP-1-analoger haft kvar mat i magen trots sådan fasta.

Förklaringen skulle kunna vara att en av de aptitdämpande effekterna av behandlingen är att magsäcken tömmer sig långsammare än normalt.

Amerikansk rekommendation

I USA har narkosläkarnas professionsförbund American societey of anesthesiologists uppmärksammat samma problem.

I somras kom organisationen därför med en särskild  rekommendation. Den säger att patienter med GLP-1-läkemedel bör pausa behandlingen inför planerade operationer som kräver sövning.

PRAC kommer under det möte som nu pågår att besluta om eventuella åtgärder till följd av signalerna om risker med aptitdämpande läkemedel vid narkos.

 

 

American Society of Anesthesiologists Consensus-Based Guidance on Preoperative Management of Patients (Adults and Children) on Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists

Girish P. Joshi, M.B.B.S., M.D., Basem B. Abdelmalak, M.D., Wade A. Weigel, M.D., Sulpicio G. Soriano, M.D., Monica W. Harbell, M.D., Catherine I. Kuo, M.D., Paul A. Stricker, M.D., Karen B. Domino, M.D., M.P.H., American Society of Anesthesiologists (ASA) Task Force on Preoperative Fasting 

Glucagon-like peptide-1 (GLP-1) receptor agonists are approved by the Food and Drug Administration for treatment of type 2 diabetes mellitus and cardiovascular risk reduction in this cohort.¹ In addition, GLP-1 receptor agonists are also used for weight loss. Several entities have recommended to hold these drugs either the day before or day of the procedure. ^2-7For patients on weekly dosing, it is recommended to hold the dose for a week.⁸ 

The GLP-1 agonists are associated with adverse gastrointestinal effects such as nausea, vomiting and delayed gastric emptying. The effects on gastric emptying are reported to be reduced with long-term use.^9,10 This is most likely through rapid tachyphylaxis at the level of vagal nerve activation.¹¹

Based on recent anecdotal reports, there are concerns that delayed gastric emptying from GLP-1 agonists can increase the risk of regurgitation and pulmonary aspiration of gastric contents during general anesthesia and deep sedation.^12-14

The presence of adverse gastrointestinal symptoms (nausea, vomiting, dyspepsia, abdominal distension) in patients taking GLP-1 agonists are predictive of increased residual gastric contents.¹²

The use of GLP-1 agonists in pediatrics has primarily been reported for the management of type 2 diabetes mellitus and obesity. The published literature on GLP-1 agonists in pediatrics is predominantly from pediatric patients 10-18 years old; concerns are similar to those reported in adults. During the conduct of general anesthesia/deep sedation, children on GLP-1 agonists have similar gastrointestinal adverse events at a rate similar to adults.

The American Society of Anesthesiologists (ASA) Task Force on Preoperative Fasting reviewed the available literature on GLP-1 agonists and associated gastrointestinal adverse effects, including the consequences of delayed gastric emptying.

The evidence to provide guidance for preoperative management of these drugs to prevent regurgitation and pulmonary aspiration of gastric contents is sparse limited only to several case reports.

Nevertheless, given the concerns of GLP-1 agonists-induced delayed gastric emptying and associated high risk of regurgitation and aspiration of gastric contents, the task force suggests the following for elective procedures. For patients requiring urgent or emergent procedures, proceed and treat the patient as ‘full stomach’ and manage accordingly.

For patients scheduled for elective procedures consider the following:

Day(s) Prior to the Procedure:

• For patients on daily dosing consider holding GLP-1 agonists on the day of the procedure/surgery. For patients on weekly dosing consider holding GLP-1 agonists a week prior to the procedure/surgery.
• This suggestion is irrespective of the indication (type 2 diabetes mellitus or weight loss), dose, or the type of procedure/surgery.
• If GLP-1 agonists prescribed for diabetes management are held for longer than the dosing schedule, consider consulting an endocrinologist for bridging the antidiabetic therapy to avoid hyperglycemia.

Day of the Procedure: 

• If gastrointestinal (GI) symptoms such as severe nausea/vomiting/retching, abdominal bloating, or abdominal pain are present, consider delaying elective procedure, and discuss the concerns of potential risk of regurgitation and pulmonary aspiration of gastric contents with the proceduralist/surgeon and the patient.
• If the patient has no GI symptoms, and the GLP-1 agonists have been held as advised, proceed as usual. 
• If the patient has no GI symptoms, but the GLP-1 agonists were not held as advised, proceed with ‘full stomach’ precautions or consider evaluating gastric volume by ultrasound, if possible and if proficient with the technique. If the stomach is empty, proceed as usual. If the stomach is full or if gastric ultrasound inconclusive or not possible, consider delaying the procedure or treat the patient as ‘full stomach’ and manage accordingly. Discuss the concerns of potential risk of regurgitation and pulmonary aspiration of gastric contents with the proceduralist/surgeon and the patient.
• There is no evidence to suggest the optimal duration of fasting for patients on GLP-1 agonists. Therefore, until we have adequate evidence, we suggest following the current ASA fasting guidelines.^15,16 

References

1. Kelsey MD, Nelson AJ, Green JB, Granger CB, Peterson ED, McGuire DK, Pagidipati NJ. Guidelines for cardiovascular risk reduction in patients with type 2 diabetes: JACC guideline comparison. J Am Coll Cardiol 2022; 79: 1849-57.
2. Crowley K, O’Scanaill P, Hermanides J, Buggy DJ. Current practice in the perioperative management of patients with diabetes mellitus: a narrative review. Br J Anaesth 2023 (epub) S0007-0912(23)00128-9.
3. American Diabetes Association Professional Practice Committee. 16. Diabetes care in the hospital: Standards of Medical Care in Diabetes—2022. Diabetes Care 2022; 45 (Suppl 1): S244–S253. 
4. American Diabetes Association. 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes-2022. Diabetes Care. 2022; 45 (Suppl 1): S125-43 
5. Grant B, Chowdhury TA. New guidance on the perioperative management of diabetes. Clin Med (Lond). 2022; 22 (1): 41-4.
6. Academy of Medical Royal Colleges. Guideline for perioperative care for people with diabetes mellitus undergoing elective and emergency surgery. London, England: Centre for Perioperative Care (CPOC); March 2021. 
7. Barker P, Creasey PE, Dhatariya K, et al. Perioperative management of the surgical patient with diabetes 2015. Anaesthesia 2015;70:1427-1440. Correction- Anaesthesia 2019;7 4: 810. 
8. Pfeifer KJ, Selzer A, Mendez CE, et al. Preoperative management of endocrine, hormonal, and urologic medications: Society for Perioperative Assessment and Quality Improvement (SPAQI) Consensus Statement. Mayo Clin Proc 2021; 96: 1655-69. 
9. Friedrichsen M, Breitschaft A, Tadayon S, Wizert A, Skovgaard D: The effect of semaglutide 2.4 mg once weekly on energy intake, appetite, control of eating, and gastric emptying in adults with obesity. Diabetes Ones Metab 2021; 23: 754-62.
10. Hjerpsted JB, Flint A, Brooks A, Axelsen MB, Kvist T, Blundell J: Semaglutide improves postprandial glucose and lipid metabolism, and delays first-hour gastric emptying in subjects with obesity. Diabetes Obes Metab 2018; 20: 610-9.
11. Nauck MA, Kemmeries G, Holst JJ, Meier JJ. Rapid tachyphylaxis of the glucagon-like peptide 1-induced deceleration of gastric emptying in humans. Diabetes 2011; 60: 1561-5.
12. Silveira SQ, da Silva LM, Abib ACV, et al. Relationship between perioperative semaglutide use and residual gastric content: A retrospective analysis of patients undergoing elective upper endoscopy. J Clin Anesth. 2023; 87: 111091. 
13. Kobori T, Onishi Y, Yoshida Y, et al. Association of glucagon-like peptide-1 receptor agonist treatment with gastric residue in an esophagogastroduodenoscopy. J Diabetes Investig. 2023; 14: 767-73.
14. Klein SR, Hobai IA. Semaglutide, delayed gastric emptying, and intraoperative pulmonary aspiration: A case report. Can J Anesth. 2023. DOI: 10.1007/s12630-023-02440-3.
15. American Society of Anesthesiologists Committee. Practice guidelines for preoperative fasting and the use of pharmacologic agents to reduce the risk of pulmonary aspiration: Application to healthy patients undergoing elective procedures. An updated report by the American Society of Anesthesiologists task force on preoperative fasting and the use of pharmacologic agents to reduce the risk of pulmonary aspiration. Anesthesiology 2017; 126:376-93.
16. Joshi GP, Abdelmalak BB, Weigel WA, et al. 2023 American Society of Anesthesiologists practice guidelines for preoperative fasting: clear liquids containing carbohydrates with or without protein, chewing gum, and pediatric fasting durations: A modular update of the 2017 American Society of Anesthesiologists Practice Guidelines for Preoperative Fasting. Anesthesiology 2023; 138:132-51.