Tachyphylaxis associated with continuous cisatracurium versus pancuronium therapy

Area of Science:

• Critical Care Medicine
• Pharmacology

Background:

• Neuromuscular blocking agents (NMBAs) are essential for mechanical ventilation in intensive care units.
• Understanding the long-term dosing requirements and potential tachyphylaxis of NMBAs is crucial for patient management and cost-effectiveness.

Purpose of the Study:

• To compare the changes in cisatracurium and pancuronium infusion requirements over time in critically ill patients.
• To identify factors influencing these dosing requirements and potential tachyphylaxis.

Main Methods:

• Retrospective comparative cohort analysis of 45 adult patients receiving continuous cisatracurium or pancuronium for at least 48 hours.
• Hierarchical linear modeling was used to analyze dosing requirements and identify confounders.
• Time-invariant and time-variant factors were assessed, including patient characteristics, ventilation settings, and laboratory values.

Main Results:

• Cisatracurium infusion rates escalated significantly more over time (0.39 microg/kg/min) than pancuronium (-0.06 microg/kg/min).
• This escalation was associated with substantially higher daily drug costs for cisatracurium ($258) compared to pancuronium ($11).
• Confounder analysis did not reveal significant differences in factors explaining the temporal dosing relationship between the two agents.

Conclusions:

• Dosing requirements for cisatracurium increase significantly over time, indicating tachyphylaxis, at a greater rate than pancuronium.
• This phenomenon is linked to considerable drug-related costs and is not explained by common patient or disease-related factors.
• Further research is needed to understand the mechanisms and risk factors for cisatracurium tachyphylaxis.