Determining the potency of neuromuscular blockers: are traditional methods flawed?

Abstract

The ED(50) is a very robust parameter. When comparing the potency of neuromuscular blockers, it is this value rather than the ED(95) that should be used. The CL for the ED(95), regardless of how it is calculated, are so wide that this parameter must be viewed, at best, as an approximation.

Neuromuscular dose–response studies: determining sample size

“…There are at least theoretical reasons to suggest that traditional linear regression analysis is a flawed approach to determining the neuromuscular doseresponse relationship. 7 Probit and logit analyses are meant to handle only quantal responses with binomial error distributions, not continuous data such as the per cent of maximal response. In addition, 0% and 100% responses are undefined when using logit or probit data transformation.…”

“…When reviewing data from a recent publication 7 in which we re-examined the dose -response relationships of succinylcholine, rocuronium, rapacuronium, and cisatracurium, we noticed that the COV of these compounds appeared to be relatively constant from agent to agent. We hypothesized that if this is so, then sample size recommendations for these agents might be generally applicable to other neuromuscular blocking drugs as well.…”

No regional difference in cisatracurium dose–response and time-course-of-action between patients in China and Bosnia

“…The latest GCRP consensus conference 14 stated that ED 50 is a far more robust parameter, and not ED 95 , and is the recommended parameter for determining NMBAs dosage. Kopman and colleagues 23 recently reanalysed raw data from previously published cisatracurium studies. They demonstrated that ED 50 calculated by non-linear regression analysis (NLR) and linear regression analysis (LRA) were interchangeable.…”

“…However, LRA resulted in ED 95 values that were 13-18% lower than those determined by NLR. 23 When plotted on arithmetic axes, NMBAs dose -response relationships take the form of sigmoid curves. However, to determine effective doses using NLR is rather complicated.…”

“…Hence, some statisticians now consider this approach to be outmoded. 23 We used the cumulative-dose technique, rather than the single-dose method, the gold standard for creating doseresponse curves, 17 as this would have required a far larger sample size. 14 The cumulative-dose technique could be used for long-acting NMBAs, provided that the incremental doses were given within a brief period of time such as the 36 s we used in our study, to allow no significant recovery between incremental doses.…”