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Multicenter Study
. 2024 Aug;38(4):464-474.
doi: 10.1007/s00540-024-03335-3. Epub 2024 Mar 17.

Incidence of sodium-glucose cotransporter-2 inhibitor-associated perioperative ketoacidosis in surgical patients: a prospective cohort study

Hiroyuki Seki  1 , Norifumi Kuratani  2 , Toshiya Shiga  3 , Yudai Iwasaki  4 , Kanae Karita  5 , Kazuki Yasuda  6 , Natsuko Yamamoto  7 , Yuko Nakanishi  8 , Kenji Shigematsu  9 , Kensuke Kobayashi  10 , Junichi Saito  11 , Ichiro Kondo  12 , Nozomu Yaida  13 , Hidenobu Watanabe  14 , Midoriko Higashi  15 , Tetsuro Shirasaka  16 , Akira Doshu-Kajiura  17 , Mitsutaka Edanaga  18 , Satoshi Tanaka  19 , Saori Ikumi  4 , Shingo Ito  20 , Masayuki Okada  21 , Tomoko Yorozu  14 ; SAPKA Investigators
Affiliations
Multicenter Study

Incidence of sodium-glucose cotransporter-2 inhibitor-associated perioperative ketoacidosis in surgical patients: a prospective cohort study

Hiroyuki Seki et al. J Anesth. 2024 Aug.

Abstract

Purpose: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) are commonly prescribed anti-diabetic medications with various beneficial effects; however, they have also been associated with ketoacidosis. The aim of this study was to determine the incidence of SGLT2i-associated perioperative ketoacidosis (SAPKA) in surgical patients.

Methods: We conducted a multicenter, prospective cohort study across 16 centers in Japan, enrolling surgical patients with diabetes who were prescribed SGLT2is between January 2021 and August 2022. Patients were monitored until the third postoperative day to screen for SAPKA, defined as urine ketone positivity with a blood pH of < 7.30 and HCO3 level ≤ 18.0 mEq/L, excluding cases of respiratory acidosis.

Results: In total, 759 of the 762 evaluated patients were included in the final analysis. Among these, three patients (0.40%) had urine ketones with a blood pH of < 7.30; however, blood gas analysis revealed respiratory acidosis in all three, and none of them was considered to have SAPKA. The estimated incidence of SGLT2i-associated postoperative ketoacidosis was 0% (95% confidence interval, 0%-0.4%).

Conclusions: The observed incidence of SAPKA in our general surgical population was lower than expected. However, given that the study was observational in nature, interpretation of study results warrants careful considerations for biases.

Keywords: Diabetes mellitus; Diabetic ketoacidosis; Prospective study; Sodium–glucose cotransporter 2 inhibitors.

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Conflict of interest statement

None. This manuscript was partly presented at the International Anesthesia Research Society Annual Meeting 2023 in Denver on 16 April 2023.

Figures

Fig. 1
Fig. 1
Study enrollment. *Among the 444 patients with negative urine ketone results, BGA was performed for 152 patients as part of routine postoperative examinations. Within this group, six instances of acidemia were identified: four of respiratory acidosis and two of metabolic acidosis. Notably, the two metabolic acidosis cases exhibited a normal anion gap. **Patients exhibited respiratory acidosis, evidenced by an elevated partial pressure of carbon dioxide and normal bicarbonate and anion gap values; no signs of ketoacidosis were detected. BGA, blood gas analysis; SAPKA, SGLT2i-associated postoperative ketoacidosis; SGLT2i, sodium–glucose cotransporter-2 inhibitor
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