Anesth Pain Med.  2022 Apr;17(2):182-190. 10.17085/apm.21076.

Effects of hydrocortisone-presensitized sugammadex on recovery from neuromuscular blockade induced by rocuronium: a rodent in vivo study

• Choi HR
• Yang HS
• Choi JM
• Park C
• In J
• Kim YB

• KMID: 2531694
• DOI: http://doi.org/10.17085/apm.21076

Abstract

Background
Sugammadex is a specific antagonist of aminosteroidal neuromuscular blocking agents with 1:1 binding to guest molecules. Sugammadex can also bind to other drugs having a steroid component in its chemical structure. In this in vivo experiment, we investigated the differences in the recovery of rocuronium-induced neuromuscular blockade using sugammadex pre-exposed with two different concentrations of hydrocortisone. Methods: The sciatic nerves and tibialis anterior muscles of 30 adult Sprague–Dawley rats were prepared for the experiment. The sciatic nerves were stimulated using a train-of-four (TOF) pattern with indirect supramaximal stimulation at 20 s intervals. After 15 min of stabilization, a 250 μg loading dose and 125 μg booster doses of rocuronium were serially administered until > 95% depression of the first twitch tension of TOF stimulation (T1) was confirmed. The study drugs were prepared by mixing sugamadex with the same volume of three different stock solutions (0.9% normal saline, 10 mg/ml hydrocortisone, and 100 mg/ ml hydrocortisone). The recovery of rats from neuromuscular blockade was monitored by assessing T1 and the TOF ratio (TOFR) simultaneously until T1 was recovered to > 95% and TOFR to > 0.9. Results: In the group injected with sugammadex premixed with a high concentration of hydrocortisone, statistically significant intergroup differences were observed in the recovery progression of T1 and TOFR (P < 0.050). Conclusions: When sugammadex was pre-exposed to a high dose of hydrocortisone only, recovery from neuromuscular blockade was delayed. Delayed recovery from neuromuscular blockade is not always plausible when sugammadex is pre-exposed to steroidal drugs.

Keyword

Hydrocortisone; Neuromuscular blockade; Neuromuscular blocking agent; Neuromuscular physiology; Rocuronium; Sugammadex

Figure

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  Fig. 1. Study protocol. SD: Sprague–Dawley, TOFR: train-of-four ratio, ED95: 95% effective dose.

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  Fig. 2. Comparison of the progression of recovery of T1. We used the equation of y = 100 + Ω(x – b)3 where y represents T1, x represents the time set from 5% T1 recovery (taken as the zero point), b represent the virtual time to > 95% T1 recovery, and Ω represent the slope of each regression curve. In (A), the T1 recovery progression in the SGX + High group (diamond, dash­dot line) was significantly delayed comparing with the control (dot, solid line), or SGX + Low (triangle, dashed line) group. In the box plot in (B), the mean value of Ω in the SGX + High (cross hatched box) was significantly lower than that of the control (hollow box), or SGX + Low (single hatched box) groups (*P = 0.001). However, there were no significant differences in Ω between the control and SGX + Low groups (P > 0.05). T1: first twitch tension of train-of-four stimulation, SGX: sugammadex.

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  Fig. 3. Comparison of the progression of TOFR recovery. We used the equation of y = 1 + λ(x – c)3 where y represents TOFR, x represents the time set from injection of the study drug (taken as the zero point), c represent the virtual time to > 0.9 TOFR, and λ represent the slope of each regression curve. In (A), the TOFR in the SGX + Low (triangle, dashed line) and SGX + High (diamond, dash-dot line) groups showed significantly slower recovery than that of the control (dot, solid line) group. In the box plot in (B), the mean value of λ in control (hollow box) group was significantly higher than that in the SGX + Low (single hatched box, P = 0.006) and SGX + High (cross hatched box, P = 0.004) groups. T1: first twitch tension of train-of-four stimulation, SGX: sugammadex, TOFR: train-of-four ratio.

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