Effects of sevoflurane anesthesia and abdominal surgery on the systemic metabolome: a prospective observational study

Abstract

Background: Metabolic status can be impacted by general anesthesia and surgery. However, the exact effects of general anesthesia and surgery on systemic metabolome remain unclear, which might contribute to postoperative outcomes.

Methods: Five hundred patients who underwent abdominal surgery were included. General anesthesia was mainly maintained with sevoflurane. The end-tidal sevoflurane concentration (ET_sevo) was adjusted to maintain BIS (Bispectral index) value between 40 and 60. The mean ET_sevo from 20 min after endotracheal intubation to 2 h after the beginning of surgery was calculated for each patient. The patients were further divided into low ET_sevo group (mean - SD) and high ET_sevo group (mean + SD) to investigate the possible metabolic changes relevant to the amount of sevoflurane exposure.

Results: The mean ET_sevo of the 500 patients was 1.60% ± 0.34%. Patients with low ET_sevo (n = 55) and high ET_sevo (n = 59) were selected for metabolomic analysis (1.06% ± 0.13% vs. 2.17% ± 0.16%, P < 0.001). Sevoflurane and abdominal surgery disturbed the tricarboxylic acid cycle as identified by increased citrate and cis-aconitate levels and impacted glycometabolism as identified by increased sucrose and D-glucose levels in these 114 patients. Glutamate metabolism was also impacted by sevoflurane and abdominal surgery in all the patients. In the patients with high ET_sevo, levels of L-glutamine, pyroglutamic acid, sphinganine and L-selenocysteine after sevoflurane anesthesia and abdominal surgery were significantly higher than those of the patients with low ET_sevo, suggesting that these metabolic changes might be relevant to the amount of sevoflurane exposure.

Conclusions: Sevoflurane anesthesia and abdominal surgery can impact principal metabolic pathways in clinical patients including tricarboxylic acid cycle, glycometabolism and glutamate metabolism. This study may provide a resource data for future studies about metabolism relevant to general anaesthesia and surgeries.

Trial registration: www.chictr.org.cn . identifier: ChiCTR1800014327 .

Keywords: Abdominal surgery; Metabonomics; Observational study; Sevoflurane.

Fig. 1

OPLS-DA score plots between the L-before and L-after groups and between the H-before and H-after groups (a, b). OPLS-DA score plots between the L-before and L-after groups and between the H-before and H-after groups (c, d)

Fig. 2

Up- and down-regulated metabolites between the L-before and L-after groups and between the H-before and H-after groups. a Heatmap of 15 metabolites with significantly different levels (5 increased and 10 decreased) between the L-before and L-after groups for individual patients. b Heatmap of 20 metabolites with significantly different levels (10 increased and 10 decreased) between the H-before and H-after groups for individual patients

Fig. 3

Up- and down-regulated metabolites among the L-before, L-after, H-before and H-after groups. a Up- and down-regulated metabolites between the L-before and L-after groups and between the H-before and H-after groups. b Up- and down-regulated metabolites between the L-before and H-before groups and between the L-after and H-after groups

Fig. 4

Correlation analysis between metabolites and AUC-ET_sevo. a Correlation analysis between 10 metabolites and AUC-ET_sevo. Four metabolites, including L-glutamine (b), L-selenocysteine (c), pyroglutamic acid (d) and sphinganine (e) were correlated with AUC-ET_sevo