Fructose-1, 6-diphosphate (FDP) as a novel antidote for yellow oleander-induced cardiac toxicity: A randomized controlled double blind study

Indika Gawarammana,Fahim Mohamed,Nick A Buckley,Shantha K Narangoda,Andrew H Dawson,Steven J Bowe,Shifa Azher,Ashoka Rathnathilake

doi:10.1186/1471-227x-10-15

Abstract

BackgroundCardiac toxicity due to ingestion of oleander plant seeds in Sri Lanka and some other South Asian countries is very common. At present symptomatic oleander seed poisoning carries a mortality of 10% in Sri Lanka and treatment of yellow oleander poisoning is limited to gastric decontamination and atropine administration. The only proven effective antidote is digoxin antibodies but these are not available for routine use because of the high cost. The main objective of this study is to investigate the effectiveness of a new and inexpensive antidote for patients with life threatening arrhythmias due oleander poisoning.Method/designWe set up a randomised double blind clinical trial to assess the effectiveness of Fructose 1, 6 diphosphate (FDP) in acute yellow oleander poisoning patients admitted to the adult medical wards of a tertiary hospital in Sri Lanka. Patients will be initially resuscitated following the national guidelines and eligible patients will be randomised to receive either FDP or an equal amount of normal saline. The primary outcome measure for this study is the sustained reversion to sinus rhythm with a heart rate greater than 50/min within 2 hours of completion of FDP/placebo bolus. Secondary outcomes include death, reversal of hyperkalaemia on the 6, 12, 18 and 24 hour samples and maintenance of sinus rhythm on the holter monitor. Analysis will be on intention-to-treat.DiscussionThis trial will provide information on the effectiveness of FDP in yellow oleander poisoning. If FDP is effective in cardiac glycoside toxicity, it would provide substantial benefit to the patients in rural Asia. The drug is inexpensive and thus could be made available at primary care hospitals if proven to be effective.Trial RegistrationCurrent Controlled trial ISRCTN71018309

Highlights

Cardiac toxicity due to ingestion of oleander plant seeds in Sri Lanka and some other South Asian countries is very common
Yellow oleander poisoning patients are managed with initial gastric decontamination methods such as gastric lavage, and activated charcoal, and administered atropine or occasionally isoprenaline to increase the heart rate
De Silva et al in their double blind randomised control trial reported that multiple doses of activated charcoal (MDAC) 50 g 6 hourly for 72 hours reduced mortality and occurrence of life-threatening arrhythmias[21]

Summary

Introduction

Cardiac toxicity due to ingestion of oleander plant seeds in Sri Lanka and some other South Asian countries is very common. Cardiac glycoside toxicity is the most common type of plant poisoning in Sri Lanka and some other South Asian countries [1,2,3]. Symptomatic cardiac glycoside poisoning carries a mortality rate of 10% in Sri Lanka [1]. FDP (CAS registry number 488-69-7; Merck monograph number 4297) is a phosphorylated sugar that is a normal physiological intermediary in glycolysis It is produced from glucose by the action of phosphofructokinase during glycolysis and is in turn broken down into pyruvate. FDP is capable of being actively transported into cells and acting as an alternative energy source to glucose [5] This can increase ATP production in circumstances where phosphofructokinase is inhibited (for example by lactate). The relative production of ATP is greater for FDP than glucose

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