# Association between the postoperative glycemic variability and mortality after craniotomy: a retrospective cohort study and development of a mortality prediction model

**Authors:** Yuanshuo Ge, Guangdong Wang, Yun Huang, Yaxin Zhang

PMC · DOI: 10.3389/fendo.2025.1613662 · Frontiers in Endocrinology · 2025-07-17

## TL;DR

This study shows that high blood sugar variability after brain surgery is linked to higher death rates and can help predict patient outcomes.

## Contribution

The study introduces a mortality prediction model using glycemic variability metrics in neurosurgical patients.

## Key findings

- Higher glycemic variability is independently associated with increased 28-day and 90-day mortality.
- Glycemic variability outperformed traditional clinical scores in predicting mortality.
- The Random Survival Forest model achieved an AUC of 0.841 and identified glycemic variability as a top predictor.

## Abstract

Glycemic variability (GV), typically quantified by the coefficient of variation (CV) and the root mean square of successive differences (rMSSD), has been recognized as a potential predictor of poor outcomes in critically ill patients. However, its prognostic value in neurosurgical populations remains unclear. This study investigated the association between postoperative GV and mortality following craniotomy.

We retrospectively analyzed 1,969 adult ICU patients who underwent cranial surgery. GV was measured using both CV and rMSSD calculated from blood glucose values during the ICU stay. The primary outcome was 28-day all-cause mortality; the secondary outcome was 90-day mortality. Multivariable Cox regression, restricted cubic splines, threshold effect analysis, and mediation analysis via blood urea nitrogen (BUN) were conducted. A Random Survival Forest (RSF) model was developed using machine learning and interpreted with SHAP values.

Higher GV, as reflected by both elevated CV and rMSSD, was independently associated with increased 28-day and 90-day mortality (CV per 10-unit HR: 1.20; rMSSD per 10-unit HR: 1.02; all P < 0.01). BUN partially mediated the association between GV and mortality. GV outperformed traditional clinical scores (SOFA, GCS, CCI) in ROC analysis (CV AUC = 0.72). The RSF model achieved an AUC of 0.841 and identified GV metrics as top predictors.

Postoperative glycemic variability, assessed by CV and rMSSD, is an independent and modifiable predictor of short- and mid-term mortality following craniotomy. These findings highlight the clinical importance of GV in postoperative risk stratification and support its integration into neurosurgical critical care.

## Full-text entities

- **Genes:** IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, ITIH2 (inter-alpha-trypsin inhibitor heavy chain 2) [NCBI Gene 3698] {aka H2P, ITI-HC2, SHAP}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}
- **Diseases:** CCI (MESH:C566784), neuroinflammatory (MESH:D000090862), congestive heart failure (MESH:D006333), infarct (MESH:D007238), intracerebral hemorrhage (MESH:D002543), mitochondrial dysfunction (MESH:D028361), traumatic brain injury (MESH:D000070642), ischemia (MESH:D007511), septic (MESH:D001170), Organ Failure (MESH:D009102), cancer (MESH:D009369), inflammation (MESH:D007249), injuries (MESH:D014947), ion pump failure (MESH:D051437), rMSSD (MESH:D011843), brain injury (MESH:D001930), cardiac dysfunction (MESH:D006331), AKI (MESH:D058186), lactic acidosis (MESH:D000140), diabetes (MESH:D003920), renal dysfunction (MESH:D007674), neurological (MESH:D009461), chronic pulmonary disease (MESH:D002908), endothelial dysfunction (MESH:D014652), GV (MESH:C537362), cerebral microcirculation (MESH:D002547), glycemic abnormalities (MESH:D000014), ventricular arrhythmias (MESH:D001145), cerebral edema (MESH:D001929), Comorbidity (MESH:D004194), critical illness (MESH:D016638), neuronal death (MESH:D009410), neurological emergencies (MESH:D004630), hyperlipidemia (MESH:D006949), Hypoglycemia (MESH:D007003), hypertension (MESH:D006973), Coma (MESH:D003128), Hyperglycemia (MESH:D006943), atrial fibrillation (MESH:D001281), cerebral hypoxia (MESH:D002534), coronary artery disease (MESH:D003324), myocardial infarction (MESH:D009203), glucose (MESH:D018149), death (MESH:D003643), sepsis (MESH:D018805)
- **Chemicals:** creatinine (MESH:D003404), ATP (MESH:D000255), potassium (MESH:D011188), propofol (MESH:D015742), nitrogen (MESH:D009584), calcium (MESH:D002118), Glucose (MESH:D005947), Oxygen (MESH:D010100), blood glucose (MESH:D001786), ondansetron (MESH:D017294), norepinephrine (MESH:D009638), glutamate (MESH:D018698), reactive oxygen species (MESH:D017382), epinephrine (MESH:D004837), nitric oxide (MESH:D009569), urea (MESH:D014508), sodium (MESH:D012964), mannitol (MESH:D008353)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12310502/full.md

## References

37 references — full list in the complete paper: https://tomesphere.com/paper/PMC12310502/full.md

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Source: https://tomesphere.com/paper/PMC12310502