Association Between Ionized Calcium Level and Neurological Outcome in Endovascularly Treated Patients with Spontaneous Subarachnoid Hemorrhage: A Retrospective Cohort Study

Background Spontaneous subarachnoid hemorrhage (SSAH) is associated with significant morbidity and mortality. Pathophysiological processes following initial bleeding are complex and not fully understood. In this study, we aimed to determine whether a low level of ionized calcium (Ca++), an essential cofactor in the coagulation cascade and other cellular processes, is associated with adverse neurological outcome, development of early hydrocephalus, and symptomatic vasospasm among patients with SSAH. Methods This was a retrospective single-center cohort study of all patients admitted for SSAH between January 1, 2009, and April 31, 2020. The primary outcome was an unfavorable neurological status at discharge, defined as a modified Rankin Scale score greater than or equal to 3. Secondary outcomes were the development of early hydrocephalus and symptomatic vasospasm. Multivariable logistic regression was performed to determine whether Ca++ was an independent predictor of these outcomes. Results A total of 255 patients were included in the final analysis. Hypocalcemia, older age, admission Glasgow Coma Scale (GCS) score, and admission Hunt-Hess classification scale (H&H) grades IV and V were independently associated with unfavorable neurological outcome, with adjusted odds ratios (ORs) of 1.93 (95% confidence interval [CI] 1.1-3.4; p = 0.02) for each 0.1 mmol L-1 decrease in the Ca++ level, 1.04 (95% CI 1.01-1.08; p = 0.02) for each year increase, 0.82 (95% CI 0.68-0.99; p = 0.04), and 6.29 (95% CI 1.14-34.6; p = 0.03), respectively. Risk factors for the development of hydrocephalus were hypocalcemia and GCS score, with ORs of 1.85 (95% CI 1.26-2.71; p = 0.002) for each 0.1 mmol L-1 decrease in the Ca++ level and 0.83 (95% CI 0.73-0.94; p = 0.005), respectively. Ca++ was not associated with symptomatic vasospasm (OR 1.04 [95% CI 0.76-1.41]; p = 0.81). Among patients with admission H&H grade I-III bleeding, hypocalcemia was independently associated with unfavorable neurological outcome at discharge, with an adjusted OR of 1.99 (95% CI 1.03-3.84; p = 0.04) for each 0.1 mmol L-1 decrease in the Ca++ level. Hypocalcemia was also an independent risk factor for the development of early hydrocephalus, with an adjusted OR of 2.95 (95% CI 1.49-5.84; p = 0.002) for each 0.1 mmol L-1 decrease in the Ca++ level. Ca++ was not associated with symptomatic vasospasm. No association was found between Ca++ and predefined outcomes among patients with admission H&H grade IV and V bleeding. Conclusions Our study shows that hypocalcemia is associated with worse neurological outcome at discharge and development of early hydrocephalus in endovascularly treated patients with SSAH. Potential mechanisms include calcium-induced coagulopathy and higher blood pressure. Trials are needed to assess whether correction of hypocalcemia will lead to improved outcomes.