Multicentre prospective observational study of sodium-glucose cotransporter-2 inhibitor-associated postoperative ketoacidosis: the SAPKA study protocol.

Abstract

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new class of antihyperglycaemic agents that promote urinary glucose excretion in the renal proximal tubule and have cardio-protective and renal-protective properties. However, there are several safety concerns related to increased risks of hypoglycaemic, urinary tract infections and ketoacidosis. Ketoacidosis is a potentially fatal complication that often presents as euglycaemic ketoacidosis during SGLT2 inhibitor treatment. Furthermore, invasive treatment and related surgical stress may increase the risk of ketogenesis. Therefore, this study aims to clarify the incidence of SGLT2 inhibitor-associated postoperative ketoacidosis (SAPKA) among patients who are receiving SGLT2 inhibitors and undergoing surgery under general anaesthesia. This multicentre, prospective, observational study will recruit 750 adult Japanese patients with diabetes who are receiving SGLT2 inhibitors and undergoing surgery under general anaesthesia. Urine samples will be collected on postoperative days 0, 1, 2 and 3. Blood gas analysis will be performed when urine ketone positivity is detected. The incidence of postoperative ketoacidosis will be identified based on urine ketone positivity and a blood pH of ≤7.3. The study will also collect data to identify risk factors for SAPKA. The study protocol has been approved by the ethics committee of Kyorin University (approval number: 785, 26 October 2020) and local ethical approval will be required at each participating centre. Study findings will be submitted to peer-reviewed journals and abstracts will be submitted to relevant national and international meetings. UMIN000042795.