Continuous versus Conventional Infusion of Amphotericin B Deoxycholate: A Meta-Analysis

Abstract

BackgroundTreatment with Amphotericin B (AmB) deoxycholate, which is still used widely, particularly in low-resource countries, has been challenged due to nephrotoxicity. We sought to study whether continuous infusion of AmB deoxycholate reduces nephrotoxicity retaining, however, the effectiveness of the drug.MethodsPubMed and Scopus databases were systematically searched to identify studies comparing the outcomes of patients receiving 24-h infusion of AmB (“continuous group”) and those receiving 2–6-h infusion of AmB (“conventional group”). Nephrotoxicity and all-cause mortality were the primary outcomes of the review, while treatment failure was the secondary outcome.ResultsFive studies met the inclusion criteria; one randomized controlled trial, two prospective cohort studies, and two retrospective cohort studies. The majority of patients were neutropenic with an underlying hematologic malignancy. All 5 studies (392 patients) provided data regarding the development of nephrotoxicity. A non-significant trend towards lower nephrotoxicity was observed for patients receiving continuous infusion of AmB compared with those receiving conventional infusion [RR = 0.61 (95% CI 0.36, 1.02)]. Four studies (365 patients) provided data regarding mortality; no relevant difference was detected between patients receiving continuous and those receiving conventional infusion of AmB [RR = 0.81 (95% CI 0.36, 1.83)]. Data on treatment failure of the two methods of administration was insufficient for meaningful conclusions.ConclusionThe available evidence from mainly non-randomized studies suggests that continuous infusion of AmB deoxycholate might offer an advantage over the conventional infusion regarding the development of nephrotoxicity, without compromising patient survival. Further randomized studies are needed to investigate this issue.

Prevenção da nefrotoxicidade da anfotericina B por meio do uso de fitomedicamentos

“…The presence of Amp-B in renal tubules results in the formation of aqueous pours in the plasma membrane, which encourages an influx of protons to the inside of the cell and, as a result, tubular acidification occurs through a reduction in the pH (15) . The vasoconstriction mechanism, along with the tubular acidification, induces the tubular injury, which may be characterized through the transmigration of proteins located in the cell membrane, in particular the Na/KATPase located on the basolateral side, which changes its location to the apical side.…”

“…In this way, the polyuria shown by the animals that receive Amp-B occurred as a response to the inhibition of the signalize to reabsorb water in the collector duct associated to the high concentration of electrolytes, which activated the tubuloglomerular feedback and intensified the vasoconstriction mechanism, leading to hypoxia and renal ischemia (3,17) . The clinical signs that characterize nephrotoxicity from Amp-B are acidosis, hypocalemia, depletion of magnesium and sodium, and polyuria (4,15) , which can be described as adverse effect related to the medication. According to the concepts of quality and safety in healthcare, adverse reactions to medication are described as most commonly result of errors in medication -and are also considered as preventable causes during the process of drugs administration (18) .…”

Efeito protetor da diosmina e hesperidina na nefrotoxidade induzida pela anfotericina B

“…Por outro lado, seus eventos adversos, como a nefrotoxicidade, exigem da equipe multidisciplinar conhecimento e cuidado singulares com a sua indicação e infusão endovenosa (35) .…”

“…Por outro lado, a introdução de novas terapêuticas antifúngicas não demonstrou redução na taxa de mortalidade. Além disso demonstraram custos mais elevados, limitando seu emprego em regiões com recursos financeiros mais restritos (35) . Esse cenário continua a reiterar a utilização da Anf-B como medicamento de primeira escolha para o tratamento de IFIs em nosso país.…”

“…O segundo pilar que consiste no "ao lado do leito" ou bedside inclui estudos que avaliam a efetividade, aceitabilidade e custo/benefício das intervenções das ciências clínicas (36) , seria então o "teste clínico" dos dados vindas da pesquisa básica. Exemplificando essa segunda etapa, estudo publicado por por Falagas ME et al (2013) demonstrou, por meio de uma meta-análise, que a administração contínua da Anf-B lipossomal resultou em menor nefrotoxicidade do que a Anf-B convencional em pacientes (35) . No último pilar, back again, todas as informações originadas nas etapas anteriores e a vivência clínica que consistiram em evidências fortes são convertidas em tratamentos e estratégias de prevenção que norteiam as políticas de saúde (36) .…”