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Standardized electrolyte supplementation and fluid management improves survival during amphotericin therapy for cryptococcal meningitis in resource-limited settings.

Abstract：

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.

journal_name

Open Forum Infect Dis

journal_title

Open forum infectious diseases

authors

Bahr NC,Rolfes MA,Musubire A,Nabeta H,Williams DA,Rhein J,Kambugu A,Meya DB,Boulware DR

doi

10.1093/ofid/ofu070

subject

Has Abstract

pub_date

2014-08-25 00:00:00

pages

ofu070

issue

issn

2328-8957

pii

ofu070

journal_volume

pub_type

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Standardized electrolyte supplementation and fluid management improves survival during amphotericin therapy for cryptococcal meningitis in resource-limited settings.