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

Abstract

Background: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

Keywords: cerebral perfusion pressure; cryptococcal meningitis; intracranial pressure; mean arterial pressure.

Figure 1.

Scatterplot by systolic blood pressure, CSF opening pressure, and CPP. Scatterplot of individual measurements by systolic blood pressure, CSF opening pressure, and CPP. 1 = Uncompensated intracranial hypertension: low CPP, low MAP, high ICP. 2 = Compensated intracranial hypertension: normal CPP, high MAP, high ICP. 3 = Cerebral hypoperfusion: low CPP, low MAP. 4: Cerebral hyperperfusion; high CPP, high MAP.

Figure 2.

Two-week mortality by baseline (A) CPP and (B) MAP.

Figure 3.

Proposed framework for cerebral autoregulation in cryptococcal meningitis. Figure adapted and modified from Toth et al [16]. Proposed model illustrating changes in cerebral autoregulation in the setting of cryptococcal meningitis. When autoregulatory function is intact (normal autoregulation), despite changes in CPP, cerebral blood flow is maintained at a constant level. When cerebral autoregulation is impaired, we postulate that the curve is rightward shifted (impaired autoregulation) such that higher perfusion pressures are needed to maintain cerebral blood flow. When perfusion pressure decreases below a new set critical point, cerebral hypoperfusion and ischemia ensue. When cerebral autoregulation is completely exhausted (blue line), cerebral blood flow passively changes in response to changing CPP. Elevated CPPs, leading to increased intravascular pressure, may induce fluid to leak from blood vessels into surrounding brain tissue, contributing to cerebral edema.

Figure 4.

Clinical management of cryptococcal meningitis by baseline CPP. The proposed management algorithm is based on an initial CPP (CPP = MAP – ICP) measurement and corresponding clinical correlations.