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

BACKGROUND: Traditionally, the clinical potency of neuromuscular blocking drugs has been measured using linear regression analysis (LRA) after log dose and probit or logit data transformation. However, probit and logit analyses are meant to handle only quantal responses with binomial error distributions, not continuous data such as per cent of maximal response. Some statisticians now consider this approach outmoded and assert that non-linear regression (NLR) is the preferred way to analyse sigmoidal dose-response relationships. We were interested in the degree to which the method of regression analysis alters calculated ED(50) and ED(95) values.

METHODS: We analysed raw data for succinylcholine, rocuronium, rapacuronium, and cisatracurium from previously published studies using both LRA and NLR to determine the ED(50) and ED(95) values and the respective slopes of the dose-response relationships. We also estimated drug potency using the Hill equation (HE) using the slopes obtained from LRA and NLR.

RESULTS: ED(50) values calculated by NLR, LRA, or the HE were interchangeable. LRA resulted in ED(95) values that were 13-18% lower than those determined by NLR. The 95% confidence limits (CL) for the ED(50) did not exceed +/-8% of the estimated value no matter how it was calculated vs +/-20-30% for the ED(95).

CONCLUSIONS: 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.