Effects of adenosine receptor agonist on the rocuroniuminduced neuromuscular block and sugammadex-induced recovery

Abstract

Background: Several types of receptors are found at neuromuscular presynaptic membranes. Presynaptic inhibitory A1 and facilitatory A2A receptors mediate different modulatory functions on acetylcholine release. This study investigated whether adenosine A1 receptor agonist contributes to the first twitch tension (T1) of train-of-four (TOF) stimulation depression and TOF fade during rocuronium-induced neuromuscular blockade, and sugammadex-induced recovery.

Methods: Phrenic nerve-diaphragm tissues were obtained from 30 adult Sprague-Dawley rats. Each tissue specimen was randomly allocated to either control group or 2-chloroadenosine (CADO, 10 μM) group. One hour of reaction time was allowed before initiating main experimental data collection. Loading and boost doses of rocuronium were sequentially administered until > 95% depression of the T1 was achieved. After confirming that there was no T1 twitch tension response, 15 min of resting time was allowed, after which sugammadex was administered. Recovery profiles (T1, TOF ratio [TOFR], and recovery index) were collected for 1 h and compared between groups.

Results: There were statistically significant differences on amount of rocuronium (actually used during experiment), TOFR changes during concentration-response of rocuronium (P = 0.04), and recovery profiles (P < 0.01) of CADO group comparing with the control group. However, at the initial phase of this experiment, dose-response of rocuronium in each group demonstrated no statistically significant differences (P = 0.12).

Conclusions: The adenosine A1 receptor agonist (CADO) influenced the TOFR and the recovery profile. After activating adenosine receptor, sugammadex-induced recovery from rocuronium-induced neuromuscular block was delayed.

Keywords: Adenosine A1-receptor; Neuromuscular junction; Neuromuscular nondepolarizing agents; Rocuronium; Sugammadex.

Fig. 1.

Study protocol. CADO: 2-Chloroadenosine, T1: the first twitch tension of train-of-four stimulation.

Fig. 2.

Concentration-response of rocuronium on T1 twitch tension depression and train-of-four (TOF) fade. (A) T1 depression equation: y = 50 +50sin(Ωx), where y represents the T1 depression, x represents the concentration of rocuronium, and Ω represents the slope of the regression curve. (B) TOFR equation: y = 1 − λx² , where λ represents the slope of the regression. Mean values of Ω and λ were compared between groups using the MannWhitney U test. Rocuronium EC₅₀ and EC₉₅ values for twitch tension data were calculated by fitting nonlinear regression curves to group data (P < 0.05). There were no statistical differences in Ω and thus in the regression curves for T1 depression between groups (P = 0.117), however, there were statistically significant differences in λ, which is the representative of the regression curve of TOFR (C, ^*P = 0.002). T1: the first twitch tension of TOF stimulation, EC₅₀: one-half maximum effective concentration, EC₉₅: effective concentration for ≥ 95% depression of T1, TOFR: the TOF ratio, CADO: 2-chloroadenosine, ROC: concentration of rocuronium at the Krebs buffer solution.

Fig. 3.

Regression of sugammadex-induced recovery from neuromuscular blockade. There was statistically significant delay in T1 recovery in the CADO group. Zero point is the time at which sugammadex was administered. Most of the specimens in the control group reached 95% T1 recovery but those in the CADO group did not. CADO: 2-chloroadenosine, T1: the first twitch tension of train-of-four stimulation.