Pharmacokinetics-Pharmacodynamics relationship of Succinylcholine and Rocuronium during Electroconvulsive Therapy

Background Neuromuscular blocking agents (NMBAs) are used during electroconvulsive therapy (ECT) to mitigate the induced severe muscle contractures. The objective of this study was to analyze the pharmacokinetics-pharmacodynamics (PK-PD) relationship of succinylcholine and rocuronium during ECT. Methods The available data on the first twitch height (T1) of 31 patients who underwent ECT as well as the corresponding intravenously applied doses of succinylcholine and rocuronium were used for the analyses in the study. The T1% (percentage change from the response to the supramaximal stimulus) derived from continuously applied TOF Watch recording to assess the minimal effective doses of succinylcholine and rocuronium during ECT. NONMEM software was used to construct, evaluate and validate the PKPD models. The PKPD of the two NMBAs was described using a two-compartment PK model and effect compartment model. The PK-PD parameter estimates required for the simulation of blood concentration were abstracted from previously reported studies in the literature. Results The PD model parameter estimates for succinlcholine and rocuronium during ECT were ke0= 0.04 min−1 (SEE=0.004) and ke0= 0.17 min-1 (SEE=0.19), respectively. The Ce50 estimations for these two NMBAs were amounted to 0.7 μg/ml (SEE=0.06) and 1.6 (SEE=0.1), respectively. The ke0 for neostigmine was not estimable, however the Ce50 was measured to be 0.412 (SEE=0.06). Conclusion The estimated PK-PD parameters for succinylcholine and rocuronium during ECT are almost comparable to previous PK-PD estimates for these two NMBA. The observed higher Ce50 for rocuronium might explain faster recovery after ECT from NMB and warrants further investigation. PK-PD of succinylcholine and rocuromium during ECT Chapter 4