Introduction: Intracerebral hemorrhage (ICH) is associated with worse clinical outcome and high mortality. Secondary mechanisms of injury promoting cerebral edema play a major role. One proposed mechanism for cerebral edema lies with sulfonylurea receptor 1 (SUR1), which is upregulated in focal cerebral ischemia and leads to passive vasogenic edema. Sulfonylureas (SFU) inhibit SUR1, and recent results of GAMES-Pilot trial indicate that they may also provide neuroprotection against malignant cerebral edema and improve clinical outcome in ischemic stroke. We sought to evaluate the association of prehospital SFU use with outcomes in diabetic (DM) patients with acute ICH.
Methods: We retrospectively analyzed a prospective cohort of patients presenting with acute (<24 hrs) ICH at a tertiary care center. Study inclusion criteria included history of DM, spontaneous ICH etiology, and age > 18 yo. Baseline ICH severity was documented using ICH-score. Hematoma volumes (HV) on admission were calculated using ABC/2 formula. Unfavorable functional outcome was documented as a mRS score of 2-6 at discharge.
Results: 230 patients with ICH and DM fulfilled inclusion criteria; 37 patients were pretreated with SFU (mean age 67 ±10 years, male 41%). Patients with SFU pretreatment had significantly (p<0.05) lower median ICH-score (1 point, IQR: 0-2) and median admission HV (4cm3, IQR:1-12) compared to controls [ICH-score: 1 point (IQR:0-3); HV: 9 cm3 (IQR:3-20)]. Unfavorable functional outcome was less common in SFU pretreated patients (49% vs 81 %; p=0.004). SFU pretreatment was independently (p=0.043) and negatively associated with the natural logarithm of admission HV (linear regression coefficient: -0.62; 95%CI: -0.02, -1.23) in multiple linear regression models adjusting for potential confounders. Pretreatment with SFU was also independently (p=0.013) associated with lower likelihood of unfavorable functional (OR: 0.12; 95%CI: 0.02, 0.64) outcome in multivariable logistic regression models adjusting for potential confounders.
Conclusions: Pretreatment with SFU may be an independent predictor for smaller hematoma volume and improved functional outcome in diabetic patients with acute ICH. This association requires independent confirmation.