Safety and Efficacy of Ketamine Versus Ketamine-Fentanyl-Dexmedetomidine Combination for Anesthesia and Analgesia in Rats

Li, Chun‐Zhu; Peng, Jiali; Hu, Rong; Jia, Yan; Sun, Yinghao; Zhang, Lei; Liu, Wenbin; Jiang, Hong

doi:10.1177/1559325819825902

Cited by 9 publications

(14 citation statements)

References 38 publications

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“…Successive administration of KFD and PNF led to a lower heart rate during anesthesia, which gradually returned to normal levels after awakening. We observed that the low heart rate of the KFD + PNF group was comparable to that of KFD in our previous study 7 . Moreover, there were no significant changes in the SpO 2 or respiratory rate of the KFD + PNF group during the detection period compared with those of the control.…”

Section: Discussionsupporting

confidence: 80%

“…In a previous study, although we showed that KFD was a safe and effective anesthetic formulation, the duration of the KFD-induced LORR was much longer than that of ketamine alone 7 , which indicated that KFD may not be suitable for short-term surgery. Therefore, reversing anesthesia with antagonists may be a method with a high anesthetic quality and a short duration of anesthesia.…”

Section: Discussionmentioning

confidence: 71%

“…In a previous study, we found that KFD did not cause side effects in the cardiovascular and respiratory systems of rats 7 . However, it is not clear whether PNF treatment will affect these systems.…”

Section: Pnf Combined With Kfd Had No Obvious Adverse Effects On the mentioning

confidence: 75%

“…at 10 mL/kg. The drug doses were selected on the basis of previous studies with slight modifications 7,18,23 . All rats consistently responded to the drugs in the same way, and we did not observe any mortality throughout the study.…”

Section: Methodsmentioning

confidence: 99%

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GluN2A-selective positive allosteric modulator-nalmefene-flumazenil reverses ketamine-fentanyl-dexmedetomidine-induced anesthesia and analgesia in rats

Jia

Tang

et al. 2020

Sci Rep

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Anesthetics are used to produce hypnosis and analgesic effects during surgery, but anesthesia for a long time after the operation is not conducive to the recovery of animals or patients. Therefore, finding appropriate treatments to counter the effects of anesthetics could enhance postoperative recovery. In the current study, we discovered the novel role of a GluN2A-selective positive allosteric modulator (PAM) in ketamine-induced anesthesia and investigated the effects of the PAM combined with nalmefene and flumazenil (PNF) in reversing the actions of an anesthetic combination (ketaminefentanyl-dexmedetomidine, KFD). PAM treatment dose-dependently decreased the duration of the ketamine-induced loss of righting reflex (LORR). Compared with those in the KFD group, the duration of LORR and the analgesic effect of the KFD + PNF group were obviously decreased. Meanwhile, successive administration of PNF and KFD had no adverse effects on the cardiovascular and respiratory systems. Both the KFD group and the KFD + PNF group showed no changes in hepatic and renal function or cognitive function in rats. Moreover, the recovery of motor coordination of the KFD + PNF group was faster than that of the KFD group. In summary, our results suggest the potential application of the PNF combination as an antagonistic treatment strategy for anesthesia. Ketamine, a noncompetitive NMDA receptor antagonist, is a dissociative general anesthetic 1,2. Fentanyl is a synthetic µ-opioid receptor agonist used as a narcotic analgesic agent in general and regional anesthesia, since it exhibits a rapid onset, a short duration, and potent analgesic effects 3,4. Dexmedetomidine, a selective α2-adrenoceptor agonist with profound sedative, analgesic, amnestic and anesthetic-sparing properties, is commonly used as an anesthetic adjuvant clinically 5,6. In a previous study, we showed that the low-dose combination of ketamine, fentanyl and dexmedetomidine (KFD) offered safer and more efficient anesthesia than ketamine alone 7. However, compared with ketamine, the KFD combination induced a longer duration of the loss of righting reflex (LORR) 7. Hence, identification of appropriate treatments to reverse the effects of anesthetics could help reduce the risk caused by prolonged unnecessary anesthesia. GNE-5729 8 , which we used in the present study, is a pyridopyrimidinone-based GluN2A subunit-selective positive allosteric modulator (PAM) of the NMDA receptor. Subunit-selective PAMs are new classes of NMDA

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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 71%

Section: Pnf Combined With Kfd Had No Obvious Adverse Effects On the mentioning

confidence: 75%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

GluN2A-selective positive allosteric modulator-nalmefene-flumazenil reverses ketamine-fentanyl-dexmedetomidine-induced anesthesia and analgesia in rats

Jia

Tang

et al. 2020

Sci Rep

Self Cite

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“…Blood samples were taken at 48 h after STZ administration, under ketamine anesthesia (5 mg/100 g bw, i.p. route) from retro-orbital sinus, followed by rat euthanasia by cervical dislocation [43]. Rats with glucose higher or equal to 200 mg/dL were considered to have diabetes mellitus [20].…”

Section: Experimental Modelmentioning

confidence: 99%

The Effect of Nano-Epigallocatechin-Gallate on Oxidative Stress and Matrix Metalloproteinases in Experimental Diabetes Mellitus

et al. 2020

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Background: The antioxidant properties of epigallocatechin-gallate (EGCG), a green tea compound, have been already studied in various diseases. Improving the bioavailability of EGCG by nanoformulation may contribute to a more effective treatment of diabetes mellitus (DM) metabolic consequences and vascular complications. The aim of this study was to test the comparative effect of liposomal EGCG with EGCG solution in experimental DM induced by streptozotocin (STZ) in rats. Method: 28 Wistar-Bratislava rats were randomly divided into four groups (7 animals/group): group 1—control group, with intraperitoneal (i.p.) administration of 1 mL saline solution (C); group 2—STZ administration by i.p. route (60 mg/100 g body weight, bw) (STZ); group 3—STZ administration as before + i.p. administration of EGCG solution (EGCG), 2.5 mg/100 g b.w. as pretreatment; group 4—STZ administration as before + i.p. administration of liposomal EGCG, 2.5 mg/100 g b.w. (L-EGCG). The comparative effects of EGCG and L-EGCG were studied on: (i) oxidative stress parameters such as malondialdehyde (MDA), indirect nitric oxide (NOx) synthesis, and total oxidative status (TOS); (ii) antioxidant status assessed by total antioxidant capacity of plasma (TAC), thiols, and catalase; (iii) matrix-metalloproteinase-2 (MMP-2) and -9 (MMP-9). Results: L-EGCG has a better efficiency regarding the improvement of oxidative stress parameters (highly statistically significant with p-values < 0.001 for MDA, NOx, and TOS) and for antioxidant capacity of plasma (highly significant p < 0.001 for thiols and significant for catalase and TAC with p < 0.05). MMP-2 and -9 were also significantly reduced in the L-EGCG-treated group compared with the EGCG group (p < 0.001). Conclusions: the liposomal nanoformulation of EGCG may serve as an adjuvant therapy in DM due to its unique modulatory effect on oxidative stress/antioxidant biomarkers and MMP-2 and -9.

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The impact of dexmedetomidine on ketamine‐induced neurotoxicity and cognitive impairment in young mice

Chai,

Jiang,

2024

Intl J of Devlp Neuroscience

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BackgroundThe potential neuroprotective effects of dexmedetomidine against ketamine‐induced neurotoxicity remain inconclusive. This study aims to investigate the influence of dexmedetomidine on ketamine‐induced neuronal apoptosis and neurodevelopmental toxicity.MethodsIn vitro experiments employed concentrations of 0.1 uM for dexmedetomidine and 50 uM for ketamine individually as well as their combination. Changes in apoptotic proteins and dendritic development in neurons were assessed after a 6‐h exposure to the drugs with evaluations conducted 24 hs' post‐treatment. In vivo experiments entailed intraperitoneal administration starting from postnatal Day 7 (P7) continuously for 3 days (P7–P9) using dosages of 100 mg/kg for ketamine and 1 mg/kg for dexmedetomidine alone or combined. Learning, memory and motor coordination abilities were evaluated via rotary rod tests and shuttle box experiments at P30 and P60, respectively.ResultsDexmedetomidine effectively mitigated ketamine‐induced apoptosis in hippocampal neurons but did not alleviate associated dendritic developmental abnormalities. Although causing reduced motor coordination in mice, no improvement was observed with regard to this effect or reaction speed when treated with dexmedetomidine alongside ketamine.ConclusionThis study demonstrates that while dexmedetomidine can mitigate ketamine‐induced neuronal apoptosis, it has limited impact on its associated neurodevelopmental toxicities.

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Safety and Efficacy of Ketamine Versus Ketamine-Fentanyl-Dexmedetomidine Combination for Anesthesia and Analgesia in Rats

Cited by 9 publications

References 38 publications

GluN2A-selective positive allosteric modulator-nalmefene-flumazenil reverses ketamine-fentanyl-dexmedetomidine-induced anesthesia and analgesia in rats

GluN2A-selective positive allosteric modulator-nalmefene-flumazenil reverses ketamine-fentanyl-dexmedetomidine-induced anesthesia and analgesia in rats

The Effect of Nano-Epigallocatechin-Gallate on Oxidative Stress and Matrix Metalloproteinases in Experimental Diabetes Mellitus

The impact of dexmedetomidine on ketamine‐induced neurotoxicity and cognitive impairment in young mice

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