Pharmacologic synergy is a phenomenon in which the interaction of two drugs creates an effect greater than the sum of effects that the two drugs would produce individually. Simply put, synergy throws math out the window and states that 1+1 is indeed greater than 2. Non-depolarizing NMBDs express synergistic effects with one another only when drugs of different structural classes are combined. Of all the non-depolarizing NMBDs structural classes, only aminosteroids (rocuronium, vecuronium, pancuronium) and benzylisoquinolones (atracurium, cisatracurium, mivacurium) include drugs that are widely used in clinical practice today. Numerous studies over the years have shown that non-depolarizing NMBDs demonstrate synergistic effects. Evidence of synergism has been shown between cisatracurium and vecuronium, cisatracurium and rocuronium, and to a lesser extent cisatracurium and mivacurium. Other studies have shown only additive effects between rocuronium and pancuronium, rocuronium and vecuronium, and rocuronium and pipecuronium. These studies all demonstrated synergy in relation to the depth of the blockade; however, there is also evidence of a synergistic increase in the length of blockade with cisatracurium given as maintenance doses after an induction dose of rocuronium. The mechanism through which this effect is mediated is unproven at this time, but is hypothesized that it is due to the differential actions of the NMBDs on pre- and post-synaptic acetylcholine receptors.
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