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

ABSTRACT

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.