The effect of therapeutic lumbar punctures on acute mortality from cryptococcal meningitis

Melissa A. Rolfes, Kathy Huppler Hullsiek, Joshua Rhein, Henry W. Nabeta, Kabanda Taseera, Charlotte Schutz, Abdu Musubire, Radha Rajasingham, Darlisha A. Williams, Friedrich Thienemann, Conrad Muzoora, Graeme Meintjes, David B. Meya, David R. Boulware

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86 Scopus citations

Abstract

Introduction. Cryptococcal meningitis is the most common cause of adult meningitis in sub-Saharan Africa. Raised intracranial pressure (ICP) is common in cryptococcosis. Prior studies suggest elevated ICP is associated with mortality, and guidelines recommend frequent lumbar punctures (LPs) to control ICP. However, the magnitude of the impact of LPs on cryptococcal-related mortality is unknown. Methods. In sum, 248 individuals with human immunodeficiency virus (HIV)-associated cryptococcal meningitis, screened for the Cryptococcal Optimal ART Timing (COAT) trial in Uganda and South Africa, were observed. Individuals received an LP to diagnose meningitis, and subsequent therapeutic LPs were recommended for elevated ICP (>250 mmH2O) or new symptoms. We compared survival, through 11 days, between individuals receiving at least 1 therapeutic LP with individuals not receiving therapeutic LPs. The COAT trial randomized subjects at 7-11 days; thus, follow-up stopped at time of death, randomization, or 11 days. Results. Seventy-five (30%) individuals had at least 1 therapeutic LP. Individuals receiving therapeutic LPs had higher cerebrospinal fluid (CSF) opening pressures, higher CSF fungal burdens, and were more likely to have altered mental status at baseline than those with no therapeutic LPs. Thirty-one deaths (18%) occurred among 173 individuals without a therapeutic LP and 5 deaths (7%) among 75 with at least 1 therapeutic LP. The adjusted relative risk of mortality was 0.31 (95% confidence interval:.12-.82). The association was observed regardless of opening pressure at baseline. Conclusions. Therapeutic LPs were associated with a 69% relative improvement in survival, regardless of initial intracranial pressure. The role of therapeutic LPs should be reevaluated.

Original languageEnglish (US)
Pages (from-to)1607-1614
Number of pages8
JournalClinical Infectious Diseases
Volume59
Issue number11
DOIs
StatePublished - Dec 1 2014

Bibliographical note

Funding Information:
Lifson, and James Neaton for their comments. They thank support from Drs Trinh Ly, Chris Lambros, Karen Reese, and Neal Wetherall. They thank institutional support from Drs Paul Bohjanen, Andrew Kambugu, Alex Coutinho, and Aaron Friedman, and the IDI DataFax team of Mariam Namawejje and Mark Ssennono for data management with support from the National Institute of Allergy and Infectious Diseases (NIAID) Office of Cyberinfrastructure and Computational Biology (OCICB), Kevin Newell, and Dr Steven Reynolds.

Keywords

  • Cryptococcal meningitis
  • Epidemiology
  • HIV
  • Mortality
  • Therapeutic lumbar punctures

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