Cerebrospinal Fluid Lactate as a Prognostic Marker of Disease Severity and Mortality in Cryptococcal Meningitis

Abstract

Background: Cerebrospinal fluid (CSF) lactate levels can differentiate between bacterial and viral meningitis. We measured CSF lactate in individuals with cryptococcal meningitis to determine its clinical significance. Methods: We measured point-of-care CSF lactate at the bedside of 319 HIV-infected Ugandan adults at diagnosis of cryptococcal meningitis. We summarized demographic variables and clinical characteristics by CSF lactate tertiles. We evaluated the association of CSF lactate with clinical characteristics and survival. Results: Individuals with high CSF lactate >5 mmol/L at cryptococcal diagnosis more likely presented with altered mental status (p<.0001), seizures (p=.0005), elevated intracranial opening pressure (p=.03), higher CSF white cells (p=0.007), and lower CSF glucose (p=.0003) compared to those with mid-range (3.1 to 5 mmol/L) or low (≤3 mmol/L) CSF lactate levels. Two-week mortality was higher among individuals with high baseline CSF lactate >5 mmol/L (35%; 38/109) as compared to individuals with mid-range (22%; 25/112) or low CSF lactate (9%; 9/97; p=<.0001). After multivariate adjustment, CSF lactate >5mmol/L remained independently associated with excess mortality (adjusted Hazard Ratio = 3.41; 95%CI, 1.55-7.51; p=.002). We found no correlation between baseline CSF lactate levels and blood capillary lactate levels (p=.72). Conclusions: Baseline point-of-care CSF lactate levels may be utilized as a prognostic marker of disease severity and mortality in cryptococcal meningitis. Individuals with an elevated baseline CSF lactate are more likely to present with altered mental status, seizures, elevated CSF opening pressures, and are at a greater risk of death. Future studies are needed to determine targeted therapeutic management strategy in persons with high CSF lactate.

Clinical Characteristics and Risk Factors for Mortality in Cryptococcal Meningitis: Evidence From a Cohort Study

“…A superior approach is to combine these two diagnostic methods. We found that seizure and altered consciousness are associated with an increased risk of 1-year death in CM, which is consistent with previous findings (19,20). Moreover, we observed that the number of symptoms shows positive correlation with the risk of death.…”