Standardized electrolyte supplementation and fluid management improves survival during amphotericin therapy for cryptococcal meningitis in resource-limited settings.
BACKGROUND
Amphotericin B is the preferred treatment for cryptococcal meningitis, but it has cumulative severe side effects, including nephrotoxicity, hypokalemia, and hypomagnesemia. Amphotericin-induced severe hypokalemia may predispose the patient to cardiac arrhythmias and death, and there is very little data available regarding these toxicities in resource-limited settings. We hypothesized that standardized electrolyte management during amphotericin therapy is essential to minimize toxicity and optimize survival in sub-Saharan Africa.


METHODS
Human immunodeficiency virus-infected, antiretroviral therapy naive adults with cryptococcal meningitis were prospectively enrolled at Mulago Hospital in Kampala, Uganda in 3 sequential cohorts with amphotericin B deoxycholate induction treatment. Intravenous fluid use was intermittent in 2001-2002, and universal in 2006-2012. In 2001-2009, serum potassium (K(+)) was monitored on days 1, 7, and 14 of treatment with replacement (K(+), Mg(2+)) per clinician discretion. In 2011-2012, K(+) was measured on days 1, 5, and approximately every 48 hours thereafter with universal electrolyte (K(+), Mg(2+)) supplementation and standardized replacement. Clinical outcomes were retrospectively compared between fluid and electrolyte management strategies.


RESULTS
With limited intravenous fluids, the 14-day survival was 49% in 2001-2002. With universal intravenous fluids, the 30-day survival improved to 62% in 2006-2010 (P = .003). In 2011-2012, with universal supplementation of fluids and electrolytes, 30-day cumulative survival improved to 78% (P = .021 vs 2006-2010 cohort). The cumulative incidence of severe hypokalemia (<2.5 mEq/L) decreased from 38% in 2010 to 8.5% in 2011-2012 with universal supplementation (P < .001).


CONCLUSIONS
Improved survival was seen in a resource-limited setting with proactive fluid and electrolyte management (K(+), Mg(2+)), as part of comprehensive amphotericin-based cryptococcal therapy.
Division of Infectious Diseases and International Medicine, Department of Medicine ; Center for Infectious Diseases and Microbiology Translational Research , University of Minnesota , Minneapolis ; Infectious Disease Institute.
Nathan C
NC
Bahr
Division of Infectious Diseases and International Medicine, Department of Medicine ; Center for Infectious Diseases and Microbiology Translational Research , University of Minnesota , Minneapolis.
Melissa A
MA
Rolfes
Infectious Disease Institute.
Abdu
A
Musubire
Infectious Disease Institute.
Henry
H
Nabeta
Division of Infectious Diseases and International Medicine, Department of Medicine ; Center for Infectious Diseases and Microbiology Translational Research , University of Minnesota , Minneapolis ; Infectious Disease Institute.
Darlisha A
DA
Williams
Division of Infectious Diseases and International Medicine, Department of Medicine ; Center for Infectious Diseases and Microbiology Translational Research , University of Minnesota , Minneapolis ; Infectious Disease Institute.
Joshua
J
Rhein
Division of Infectious Diseases and International Medicine, Department of Medicine ; Center for Infectious Diseases and Microbiology Translational Research , University of Minnesota , Minneapolis ; Infectious Disease Institute.
Andrew
A
Kambugu
Division of Infectious Diseases and International Medicine, Department of Medicine ; Center for Infectious Diseases and Microbiology Translational Research , University of Minnesota , Minneapolis ; Infectious Disease Institute ; School of Medicine, College of Health Sciences , Makerere University , Kampala , Uganda.
David B
DB
Meya
Division of Infectious Diseases and International Medicine, Department of Medicine ; Center for Infectious Diseases and Microbiology Translational Research , University of Minnesota , Minneapolis.
David R
DR
Boulware
HIV/AIDS; amphotericin; cryptococcal meningitis; potassium; side effect