Instructions to use levosimendan infusion in hospital settings

This master’s thesis examines the dosing of levosimendan in acute decompensated heart failure, with a focus on comparing the Summary of Product Characteristics (SPC) with instructions used in clinical trials and hospital guidelines for both adult and pediatric populations. The aim of this thesis is to compare how clinical practice has diverged from the SPC, particularly regarding the use of a loading bolus, and to make a recommendation on how to dose levosimendan in adults and pediatrics. The methods consisted of a systematic review of the literature and inquiry from local hospitals. Key clinical trials including RUSSLAN, LIDO, REVIVE II, SURVIVE, LeoPARDS, CHEETAH, and several pediatric studies were analyzed, alongside hospital guidelines from Australia, New Zealand, the United Kingdom and Spain. Each source was reviewed for its bolus dose, maintenance infusion rate and duration, and then compared with the Simdax SPC. The main results show that while the SPC still recommends a loading dose of 6–12 µg/kg over 10 minutes, the majority of later clinical trials and nearly all recent hospital instructions for adults have omitted the bolus dose due to its association with hypotension, as explicitly noted in the SURVIVE trial. Maintenance infusion rates of 0.05–0.2 µg/kg/min remain consistent. In pediatrics, where the drug is off-label, seven out of eight clinical trials omitted the loading dose entirely, and the Spanish Association of Pediatrics guideline follows this practice; however, some hospital guidelines still retain a bolus, often given more slowly or with a higher maximum dose. Infusion durations in pediatric trials are frequently extended beyond 24 hours, up to 72 hours, whereas adult protocols adhere to 24 hours. In conclusion, current evidence supports omitting the levosimendan loading dose in adults to reduce the risk of hypotension. In pediatrics, omitting the loading dose isn’t as clear, as most clinical trials omitted the bolus but in hospitals it was usually used. The maintenance infusion range of 0.05–0.2 µg/kg/min for 24 hours is commonly used, though pediatric patients may require longer infusions. Future research should focus on pediatric trials to establish a standardized dose.