Intravenous infusion of rocuronium bromide prolongs emergence from propofol anesthesia in rats

Abstract

Background: Neuromuscular blocking agents induce muscle paralysis via the prevention of synaptic transmission at the neuromuscular junction and may have additional effects at other sites of action. With regard to potential effects of neuromuscular blocking agents on the central nervous system, a definitive view has not been established. We investigated whether intravenous infusion of rocuronium bromide affects the emergence from propofol anesthesia.

Methods: Using an in vivo rat model, we performed propofol infusion for 60 minutes, along with rocuronium bromide at various infusion rates or normal saline. Sugammadex or normal saline was injected at the end of the infusion period, and we evaluated the time to emergence from propofol anesthesia. We also examined the neuromuscular blocking, circulatory, and respiratory properties of propofol infusion along with rocuronium bromide infusion to ascertain possible factors affecting emergence.

Results: Intravenous infusion of rocuronium bromide dose-dependently increased the time to emergence from propofol anesthesia. Sugammadex administered after propofol infusion not containing rocuronium bromide did not affect the time to emergence. Mean arterial pressure, heart rate, partial pressures of oxygen and carbon dioxide, and pH were not affected by rocuronium bromide infusion. Neuromuscular blockade induced by rocuronium bromide, even at the greatest infusion rate in the emergence experiment, was rapidly antagonized by sugammadex.

Conclusions: These results suggest that intravenous infusion of rocuronium bromide dose-dependently delays the emergence from propofol anesthesia in rats. Future studies, such as detection of rocuronium in the cerebrospinal fluid or central nervous system, electrophysiologic studies, microinjection of sugammadex into the brain, etc., are necessary to determine the mechanism of this effect.

Fig 1. Relation between time to emergence from propofol anesthesia and infusion rate of rocuronium bromide along with propofol using a linear regression model (solid line) with corresponding 95% CIs (dashed lines).

Individual responses at each dose (250, 500, 1000 μg/kg/min) are shown as black circles. The time to emergence from propofol anesthesia was dose-dependently prolonged by simultaneous infusion of rocuronium bromide (ρ = 0.624, p = 0.006).

Fig 2. Mean arterial pressure (mmHg) and heart rate (beats per minute [bpm]) measured at bolus injection of propofol (time 0) and at 1, 3, 5, 10, 20, 30, 45, and 60 min after initiating propofol infusion with rocuronium or normal saline.

(A) Mean arterial pressure after initiating propofol infusion with rocuronium did not differ significantly from that with normal saline at any time point. (B) Heart rate after initiating propofol infusion with rocuronium did not differ significantly from that with normal saline at any time point.

Fig 3. Blood gas analysis was performed at the following time points: Before infusion (Pre), at 30 min after initiation of infusion (Infusion), and at 3 min after flushing the line at the discontinuation of infusion (Post).

(A) Partial pressure of oxygen (PaO₂). (B) Partial pressure of carbon dioxide (PaCO₂). (C) pH. Values for PaO_2, PaCO₂, and pH did not differ significantly between the rocuronium group and the normal saline group at any time point.