Cerebral Perfusion Pressures and Implications on Clinical Outcomes and Medical Management in Cryptococcal Meningitis

In cryptococcal meningitis, increased intracranial pressure (ICP) is associated with worse outcomes and increased mortality. We sought to understand how changes in ICP and mean arterial pressure (MAP) affect cerebral perfusion pressure (CPP) and influence clinical outcomes. We performed a secondary data analysis of a prospective cohort of Ugandan adults with HIV-associated cryptococcal meningitis. We summarize demographic variables, clinical presentation, and 2-week survival by CPP and MAP groups. Among 593 participants, 41% had low CPP <70 mm Hg, 54% had normal CPP 70-100 mm Hg, and 5% had high CPP >100 mm Hg. There was no association between baseline CPP and 2-week mortality. As a time-varying covariate, we observed a 39% increased risk of 2-week mortality with CPP levels <70 or >100 mm Hg (hazard ratio [HR] 1.39; 95% confidence interval [CI] 1.02-1.88, P = .04). Among 686 participants with baseline MAP measurements, there was an increased risk of 2-week mortality among people with low MAP <70 mm Hg (HR 1.80; 95% CI 1.01-3.20; P = .047) or high MAP >100 mm Hg (HR 1.47; 95% CI 1.08-1.99; P = .014) compared with normal MAP 70-100 mm Hg. We identified 4 clinical profiles based on MAP, CPP, and ICP measurements: (1) uncompensated intracranial hypertension (low CPP, elevated ICP, and low MAP), (2) compensated intracranial hypertension (normal CPP, elevated ICP, and MAP), (3) cerebral hypoperfusion (low CPP and low MAP), and (4) cerebral hyperperfusion (high CPP and high MAP). In cryptococcal meningitis, there is an intricate relationship between ICP, MAP, and CPP. We provide a concept framework using data from a clinical cohort and recommendations for clinical management.