Pancuronium enhances isoflurane anesthesia in rats via inhibition of cerebral nicotinic acetylcholine receptors

Miyazaki, Yusuke; Sunaga, Hiroshi; Hobo, Shotaro; Miyano, Kazuko; Uezono, Shoichi

doi:10.1007/s00540-016-2178-1

Cited by 3 publications

(5 citation statements)

References 24 publications

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“…The effect of NMBAs on the central nervous system (CNS) is a topic of investigation. We reported that pancuronium injected into the lateral ventricle in rats dose-dependently enhanced the depth of iso urane anesthesia [1]. Our results suggested that the mechanism might be inhibition of neuronal nicotinic acetylcholine receptor transmission in the cerebrum.…”

Section: Introductionmentioning

confidence: 50%

“…It is unknown what the effects of NMBAs administered via IV infusion might be if they should pass across the BBB. The effects of NMBAs administered directly to the CSF or brain slices have been reported [1,2,6,7], and the results imply that NMBAs act on several locations in the cerebrum and have a variety of effects. We previously reported that microinjection of pancuronium into the lateral ventricle at doses of 1.6-16% of the ED 50 for NMB in rats dose-dependently enhanced the depth of iso urane anesthesia [1].…”

Section: Discussionmentioning

confidence: 98%

“…Previous studies suggest that NMBAs act at several locations in the cerebrum and have a variety of effects when administered directly to the CSF or CNS [1,2,6,7]. The effects of NMBAs when passed across the BBB after IV administration remain unclear.…”

Section: Introductionmentioning

confidence: 99%

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Effect of intravenous infusion of rocuronium on emergence from propofol anesthesia in rats

Suzuki

Sunaga

Yamakawa

et al. 2020

Preprint

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Background: Central nervous system effects of neuromuscular blocking agents have been indicated in some case reports. We investigated whether intravenous (IV) infusion of rocuronium affects emergence from propofol anesthesia in rats.Methods: We used Sprague Dawley rats. Propofol infusion was initiated with a bolus of 15 mg/kg and continued at a rate of 40 mg/kg/h. For the rocuronium group (n = 18), rocuronium was administered as an initial IV bolus of 5 mg/kg followed by continuous infusion at a rate of 250, 500, or 1000 μg/kg/min along with propofol infusion. Infusion was continued for 60 min, and sugammadex (32 mg/kg) was injected at the end of infusion. In a separate group of rats (n = 12), normal saline was administered along with propofol infusion. After continuous infusion for 60 min, normal saline or sugammadex (32 mg/kg) was injected. The time to emergence from propofol anesthesia was evaluated. To ascertain possible factors affecting emergence, the neuromuscular blocking, circulatory, and respiratory properties of IV rocuronium infusion at 1000 μg/kg/min were assessed (n = 18).Results: The time to emergence from propofol anesthesia was 239 ± 94 s after simultaneous infusion of normal saline without rocuronium and was 346 ± 78, 518 ± 134, and 638 ± 219 s after IV infusion of rocuronium at 250, 500, and 1000 μg/kg/min, respectively. The simultaneous IV infusion of rocuronium dose-dependently increased the time to emergence (ρ = 0.624; p = 0.006). Sugammadex alone did not delay emergence (280 ± 60 s; p = 0.39). Neuromuscular blockade induced by rocuronium at 1000 μg/kg/min was completely antagonized at 99 ± 21 s by sugammadex (32 mg/kg). Mean arterial pressure, heart rate, partial pressures of oxygen and carbon dioxide, and pH were not affected by rocuronium infusion.Conclusions: Our results show that IV infusion of rocuronium delays the emergence from propofol anesthesia in rats, despite the complete recovery from neuromuscular blockade by sugammadex. The use of neuromuscular blocking agents in neonates or patients with cerebrovascular diseases, whose blood-brain barrier might be immature or disrupted, should be carefully considered.

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Section: Introductionmentioning

confidence: 50%

Section: Discussionmentioning

confidence: 98%

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Effect of intravenous infusion of rocuronium on emergence from propofol anesthesia in rats

Suzuki

Sunaga

Yamakawa

et al. 2020

Preprint

Self Cite

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“…The effects of NMBAs administered directly to the cerebrospinal fluid or brain slices have been reported [20][21][22][23], and the results imply that NMBAs act at several locations in the cerebrum and have a variety of effects. We previously reported that microinjection of pancuronium into the lateral ventricle at doses of 1.6% to 16% of the ED 50 for NMB in rats dose-dependently enhanced the depth of isoflurane anesthesia [20]. Another study reported pancuronium-induced seizures when a dose of 2.3 times the ED 50 for NMB was injected into the lateral ventricle in rats [21].…”

Section: Plos Onementioning

confidence: 98%

“…Sugammadex should have removed rocuronium from the CNS in the present study. Nevertheless, because the CNS has greater sensitivity to NMBAs [20], even a small number of rocuronium molecules remaining in the CNS after intravenous injection of sugammadex might have acted to slow the recovery of awareness during emergence.…”

Section: Plos Onementioning

confidence: 99%

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

et al. 2021

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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.

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Application of neuromuscular blockade using Rocuronium for performing different surgeries and its reversal by Neostigmine-Glycopyrrolate combination in dogs

RANA

Kumar

et al. 2023

Indian J of Anim Sci

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This study was executed in the clinical setup to investigate the effects of Rocuronium and its reversal by Neostigmine and Glycopyrrolate (Myopyrolate) combination in Propofol-Isoflurane anaesthetized dogs. Rocuronium-induced neuromuscular blockade was applied to 21 clinical cases. Out of which, 19 cases were of orthopaedic surgeries and 2 cases of ovariohysterectomy. After the animal had stabilized on the mixture of isoflurane and oxygen, the relaxation of muscle was induced using Rocuronium @ 0.5 mg/kg b.wt. Immediately IPPV was provided in volume control mode. Neuromuscular blockade was reversed using a single syringe combination drug having both Neostigmine and Glycopyrrolate (Myopyrolate) @ 0.05 mg/kg b.wt and @ 0.01 mg/kg b.wt, respectively. Rocuronium caused the centering of the ocular globe gradually in less than 30 sec. During orthopaedic surgeries, the reduction of fractured ends became easy without much tissue trauma. In ovariohysterectomy surgeries, the appropriate level of abdominal muscle relaxation further helped in the easy exteriorization of the ovarian stump. The onset time for Rocuronium was 17.64±1.10 sec and its duration of action was 27.82±0.72 min. The use of Rocuronium along with IPPV caused minimal alteration of the physiological parameters with no clinical consequences and thus can be considered a complication-free anaesthetic protocol for interventions demanding muscle relaxation.

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Pancuronium enhances isoflurane anesthesia in rats via inhibition of cerebral nicotinic acetylcholine receptors

Cited by 3 publications

References 24 publications

Effect of intravenous infusion of rocuronium on emergence from propofol anesthesia in rats

Effect of intravenous infusion of rocuronium on emergence from propofol anesthesia in rats

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

Application of neuromuscular blockade using Rocuronium for performing different surgeries and its reversal by Neostigmine-Glycopyrrolate combination in dogs

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