Ketamine concentrations during cardiopulmonary bypass

McLean, R F; Baker, Andrew J.; Walker, Scott; Mazer, C. David; Wong, Benny; Harrington, Ellen

doi:10.1007/bf03011770

Cited by 16 publications

(12 citation statements)

References 25 publications

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“…Metabolic species differences could also underlie this apparent dissociation. For example, the half-life of ketamine is just 13 min in a variety of mouse lines (Maxwell et al 2006) compared to 1.4-3 h in humans (McLean et al 1996). Methods like those employed by Majewski-Tiedeken et al (2008) to sustain the acute effects of ketamine may be required to reliably mimic effective human treatments in mice.…”

Section: Discussionmentioning

confidence: 98%

CD-1 and Balb/cJ mice do not show enduring antidepressant-like effects of ketamine in tests of acute antidepressant efficacy

et al. 2011

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Section: Discussionmentioning

confidence: 98%

CD-1 and Balb/cJ mice do not show enduring antidepressant-like effects of ketamine in tests of acute antidepressant efficacy

et al. 2011

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“…Although it was reported that peak blood levels of ketamine could be as high as 103 μM, 23 the levels required to maintain anesthesia are usually in the range of 10–20 μM. 24 Experimental evidence provided from in vitro cell culture and in vivo animal studies demonstrated that ketamine could induce neurotoxicity when administered at high doses and/or for prolonged periods. 25–29 Thus, in this study, we treated neurons with ketamine (100 μM) to study the effect of ketamine on the NSC proliferation and neuronal apoptosis for 3, 6, and 24 h. The underlying mechanisms of this side effect were investigated by exposing neurons to ketamine for 24 h.…”

Section: Methodsmentioning

confidence: 99%

Ketamine Enhances Human Neural Stem Cell Proliferation and Induces Neuronal Apoptosis via Reactive Oxygen Species–Mediated Mitochondrial Pathway

Bai

Yan²,

Canfield³

et al. 2013

Anesthesia &Amp; Analgesia

169

155

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Background Growing evidence indicates that ketamine causes neurotoxicity in a variety of developing animal models, leading to a serious concern regarding the safety of pediatric anesthesia. However, if and how ketamine induces human neural cell toxicity is unknown. Recapitulation of neurogenesis from human embryonic stem cells (hESCs) in vitro allows investigation of the toxic effects of ketamine on neural stem cells (NSCs) and developing neurons which is impossible to perform in humans. In the present study we assessed the influence of ketamine on the hESC-derived NSCs and neurons. Methods hESCs were directly differentiated into neurons via NSCs. NSCs and two-week-old neurons were treated with varying doses of ketamine for different durations. NSC proliferation capacity was analyzed by Ki67 immunofluorescence staining and bromodeoxyurindine assay. Neuroapoptosis was analyzed by TUNEL staining and caspase 3 activity measurement. The mitochondria-related neuronal apoptosis pathway including mitochondrial membrane potential, cytochrome c distribution within cells, mitochondrial fission, and reactive oxygen species (ROS) production were also investigated. Results Ketamine (100 μM) increased NSC proliferation after 6 h exposure. However, significant neuronal apoptosis was only observed after 24 h of ketamine treatment. In addition, ketamine decreased mitochondrial membrane potential and increased cytochrome c release from mitochondria into cytosol. Ketamine also enhanced mitochondrial fission as well as ROS production compared with no-treatment control. Importantly, Trolox, a ROS scavenger, significantly attenuated the increase of ketamine-induced ROS production and neuronal apoptosis. Conclusions These data for the first time demonstrate that (1) ketamine increases NSC proliferation and causes neuronal apoptosis; (2) mitochondria are involved in ketamine-induced neuronal toxicity which can be prevented by Trolox; and (3) the stem cell-associated neurogenesis system may provide a simple and promising in vitro model for rapidly screening anesthetic neurotoxicity and studying the underlying mechanisms as well as prevention strategies to avoid this toxic effect.

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“…It was reported that peak blood levels of ketamine were as high as 108 μM [18]. Ketamine levels required to maintain anesthesia were approximately 10–20 μM [19]. In addition, experimental evidence from in vitro cell culture and in vivo animal studies demonstrated that ketamine could induce neurotoxicity when administered at high doses and/or for prolonged periods [20–24].…”

Section: Methodsmentioning

confidence: 99%

Ketamine Induces Toxicity in Human Neurons Differentiated from Embryonic Stem Cells via Mitochondrial Apoptosis Pathway

Bošnjak

Yan²,

Canfield³

et al. 2012

CDS

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Ketamine is widely used for anesthesia in pediatric patients. Growing evidence indicates that ketamine causes neurotoxicity in a variety of developing animal models. Our understanding of anesthesia neurotoxicity in humans is currently limited by difficulties in obtaining neurons and performing developmental toxicity studies in fetal and pediatric populations. It may be possible to overcome these challenges by obtaining neurons from human embryonic stem cells (hESCs) in vitro. hESCs are able to replicate indefinitely and differentiate into every cell type. In this study, we investigated the toxic effect of ketamine on neurons differentiated from hESCs. Two-week-old neurons were treated with different doses and durations of ketamine with or without the reactive oxygen species (ROS) scavenger, Trolox. Cell viability, ultrastructure, mitochondrial membrane potential (ΔΨ m ), cytochrome c distribution within cells, apoptosis, and ROS production were evaluated. Here we show that ketamine induced ultrastructural abnormalities and dose-and timedependently caused cell death. In addition, ketamine decreased ΔΨ m and increased cytochrome c release from mitochondria. Ketamine also increased ROS production and induced differential expression of oxidative stress-related genes. Specifically, abnormal ultrastructural and ΔΨ m changes occurred earlier than cell death in the ketamine-induced toxicity process. Furthermore, Trolox significantly decreased ROS generation and attenuated cell death caused by ketamine in a dose-dependent manner. In conclusion, this study illustrates that ketamine time-and dosedependently induces human neurotoxicity via ROS-mediated mitochondrial apoptosis pathway and that these side effects can be prevented by the antioxidant agent Trolox. Thus, hESC-derived neurons might provide a promising tool for studying anesthetic-induced developmental neurotoxicity and prevention strategies.

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Ketamine concentrations during cardiopulmonary bypass

Abstract: Purpose: To describe the serum concentrations of ketamine following a clinically relevant dosing schedule during cardiopulmonary bypass ( C P B ). Methods:

Cited by 16 publications

References 25 publications

CD-1 and Balb/cJ mice do not show enduring antidepressant-like effects of ketamine in tests of acute antidepressant efficacy

CD-1 and Balb/cJ mice do not show enduring antidepressant-like effects of ketamine in tests of acute antidepressant efficacy

Ketamine Enhances Human Neural Stem Cell Proliferation and Induces Neuronal Apoptosis via Reactive Oxygen Species–Mediated Mitochondrial Pathway

Ketamine Induces Toxicity in Human Neurons Differentiated from Embryonic Stem Cells via Mitochondrial Apoptosis Pathway

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