Ketamine Anesthesia

[Guest guest]

Hi all,

My child have to do some dental work which requiered ANESTHESIA CALL KETAMINE, has someone use this before?

Any feedback or advise.

Many Thanks

[Guest guest]

You ask a good question. The issue of anesthesia and kids with autism is not an easy one! This article discussing anesthesia and kids with ASD was published in Autism File Magazine: http://www.mitoaction.org/files/Risk%20of%20Anesthesia%20Regression%20(2).pdf Here is some more information regarding anesthesia: http://www.mitoaction.org/autism/december-2011-teleconference My question would be, is

is absolutely necessary to use anesthesia. Can it be done with novacaine? I know one child who regressed terribly using Ketamine and Propofol:http://www.mitoaction.org/files/AlyssaDavi.pdf A critical question for the Md's would be whether the ketamine is going to be combined with something else... Some parents whose children are requiring anesthesia for dental work are having the work done in a hospital... so the child's BIS rate (level of sedation) can be closely monitored. The problem with anesthesia in kids with mitochondrial dysfunction and autism is that they may need only 10% of the typical volitle anesthesia to achieve sedation... most likely because they have reduced

energy at a cellular level. So when a child has an adverse anesthesia reaction, it is frequently due to over-sedation, that affects mitochondrial function and energy production. Controling the duration of your child's fast (you want it to be as little as possible- be the first proceedure of the day!) and monitoring glucose levels is another issue to discuss with your MD. Hope that helps,Alyssa Found these recent abstracts regarding ketamine: Curr Drug Saf. 2012 Apr;7(2):106-19.Ketamine induces

toxicity in human neurons differentiated from embryonic stem cells via mitochondrial apoptosis pathway.Bosnjak ZJ, Yan Y, Canfield S, Muravyeva MY, Kikuchi C, Wells CW, Corbett JA, Bai X.SourceDepartment of Anesthesiology, The Medical College of Wisconsin, Milwaukee, 53226, USA.AbstractKetamine 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 (ΔΨm), cytochrome c distribution within cells, apoptosis, and ROS production were evaluated. Here we show that ketamine induced ultrastructural abnormalities and dose- and time-dependently caused cell death. In addition, ketamine decreased ΔΨm 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 ΔΨm 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 dose-dependently induces human neurotoxicity at supraclinical concentrations 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.PMID: 22873495 J Mol Neurosci. 2012 May;47(1):67-75. doi: 10.1007/s12-1. Epub 2011 Dec 8.Protective function of nicotinamide against ketamine-induced apoptotic neurodegeneration in the infant rat brain.Ullah N, Ullah I, Lee HY, Naseer MI, Seok PM, Ahmed J, Kim MO.SourceDepartment of Biology, College of Natural Sciences-RINS and Applied Life Science-Brain Korea 21, Gyeongsang National University, Chinju 660-701, Republic of Korea.AbstractDuring development, anesthetics activate neuroapoptosis and produce damage in the central nervous system that leads to several types of neurological disorders. A single dose of ketamine (40 mg/kg) during synaptogenesis in a 7-day-old rat brain activated the apoptotic cascade and caused extensive neuronal cell death in the forebrain. In this study, we investigated the protective effect of nicotinamide against ketamine-induced apoptotic neurodegeneration. After 4 h, neuronal cell death induced by ketamine was associated with the induction of Bax, release of cytochrome c into the cytosol, and activation of caspase-3. One

single dose of 1 mg/g nicotinamide was administered to a developing rat and was found to inhibit ketamine-induced neuroapoptosis by downregulating Bax, inhibiting cytochrome c release from mitochondria into cytosol, and inhibiting the expression of activated caspase-3. TUNEL and immunohistochemical analyses showed that ketamine-induced cell death occurred through apoptosis and that it was inhibited by nicotinamide. Fluoro-Jade-B staining demonstrated an increased number of dead cells in the cortex and thalamus after ketamine treatment; treatment with nicotinamide reduced the number of dead cells in these brain regions. Our findings suggest that nicotinamide attenuated ketamine-induced neuronal cell loss in the developing rat brain and is a promising therapeutic and neuroprotective agent for the

treatment of neurodevelopmental disorders.PMID: 22160932 Metab Brain Dis. 2011 Mar;26(1):69-77. doi: 10.1007/s11-1. Epub 2011 Feb 18.Behavioral changes and mitochondrial dysfunction in a rat model of schizophrenia induced by ketamine.de Oliveira L, Fraga DB, De Luca RD, Canever L, Ghedim FV, Matos MP, Streck EL, Quevedo J, Zugno AI.SourceLaboratory of Neurosciences and National Institute for Translational Medicine (INCT-TM), Postgraduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, 88806-000 Criciúma, SC, Brazil.AbstractEvidence from the literature indicates that mitochondrial dysfunction occurs in schizophrenia and other psychiatric disorders. To produce an animal model that simulates psychotic symptoms analogous to those seen in schizophrenic patients, sub-anesthetic doses of

N-methyl-D-aspartate (NMDA) receptor antagonists (such as ketamine) have been used. The aim of this study was to evaluate behavioral changes and mitochondrial dysfunction in rats administered ketamine for 7 consecutive days. Behavioral evaluation was performed using an activity monitor 1, 3 and 6 h after the last injection. The activities of mitochondrial respiratory chain complexes I, II, I-III and IV in multiple brain regions (prefrontal cortex, striatum and hippocampus) were also evaluated. Our results showed that hyperlocomotion occurred in the ketamine group 1 and 3 h after the last injection. Stereotypic movements were elevated only when animals were evaluated 1 h after receiving ketamine. In addition, we found that ketamine administration affects the respiratory chain, altering the activity of

respiratory chain complexes in the striatum and hippocampus after 1 h, those in the prefrontal cortex and hippocampus after 3 h and those in the prefrontal cortex and striatum 6 h after the last administration of ketamine. These findings suggest that ketamine alters the behavior of rats and changes the activity of respiratory chain complexes in multiple brain regions at different time points.PMID: 21331561Br J Anaesth. 2010 Sep;105(3):347-54. doi: 10.1093/bja/aeq169. Epub 2010 Jul 21.Ketamine induces apoptosis via the mitochondrial

pathway in human lymphocytes and neuronal cells.Braun S, Gaza N, Werdehausen R, Hermanns H, Bauer I, Durieux ME, Hollmann MW, s MF.SourceDepartment of Anesthesiology, University of Düsseldorf, Germany.AbstractBACKGROUND: Ketamine has been shown to have neurotoxic properties, when administered neuraxially. The mechanism of this local toxicity is still unknown. Therefore, we investigated the mechanism of cytotoxicity in

different human cell lines in vitro.METHODS: We incubated the following cell types for 24 h with increasing concentrations of S(+)-ketamine and racemic ketamine: (i) human Jurkat T-lymphoma cells overexpressing the antiapoptotic B-cell lymphoma 2 protein, (ii) cells deficient of caspase-9, caspase-8, or Fas-associated protein with death domain and parental cells, and (iii) neuroblastoma cells (SHEP). N-Methyl-d-aspartate (NMDA) receptors and caspase-3 cleavage were identified by immunoblotting. Cell viability and apoptotic cell death were evaluated flowcytometrically by Annexin V and 7-aminoactinomycin D double staining. Mitochondrial metabolic activity and caspase-3 activation were measured.RESULTS: Ketamine, in a concentration-dependent manner, induced apoptosis in

lymphocytes and neuroblastoma cell lines. Cell lines with alterations of the mitochondrial pathway of apoptosis were protected against ketamine-induced apoptosis, whereas alterations of the death receptor pathway did not reduce apoptosis. S(+)-Ketamine and racemic ketamine induced the same percentage of cell death in Jurkat cells, whereas in neuroblastoma cells, S(+)-ketamine was slightly less toxic.CONCLUSIONS: Ketamine at millimolar concentrations induces apoptosis via the mitochondrial pathway, independent of death receptor signalling. At higher concentrations necrosis is the predominant mechanism. Less toxicity of S(+)-ketamine was observed in neuroblastoma cells, but this difference was minor and therefore unlikely to be

mediated via the NMDA receptor.PMID: 20659914 To: "neurosensorycentersforkids " <neurosensorycentersforkids >; "katyAutismsupport@..."

; "mb12valtrex " <mb12valtrex > Sent: Thursday, January 17, 2013 12:30 PM Subject: Ketamine "Anesthesia"

Hi all,

My child have to do some dental work which requiered ANESTHESIA CALL KETAMINE, has someone use this before?

Any feedback or advise.

Many Thanks

[Guest guest]

Thank you Alyssa for the information. That very helpful.

To: "mb12valtrex " <mb12valtrex > Sent: Thursday, January 17, 2013 11:58 AMSubject: Re: Ketamine "Anesthesia"

You ask a good question. The issue of anesthesia and kids with autism is not an easy one!

This article discussing anesthesia and kids with ASD was published in Autism File Magazine:

http://www.mitoaction.org/files/Risk%20of%20Anesthesia%20Regression%20(2).pdf

Here is some more information regarding anesthesia:

http://www.mitoaction.org/autism/december-2011-teleconference

My question would be, is is absolutely necessary to use anesthesia. Can it be done with novacaine?

I know one child who regressed terribly using Ketamine and Propofol:

http://www.mitoaction.org/files/AlyssaDavi.pdf

A critical question for the Md's would be whether the ketamine is going to be combined with something else...

Some parents whose children are requiring anesthesia for dental work are having the work done in a hospital... so the child's BIS rate (level of sedation) can be closely monitored. The problem with anesthesia in kids with mitochondrial dysfunction and autism is that they may need only 10% of the typical volitle anesthesia to achieve sedation... most likely because they have reduced energy at a cellular level. So when a child has an adverse anesthesia reaction, it is frequently due to over-sedation, that affects mitochondrial function and energy production. Controling the duration of your child's fast (you want it to be as little as possible- be the first proceedure of the day!) and monitoring glucose levels is another issue to discuss with your MD.

Hope that helps,

Alyssa

Found these recent abstracts regarding ketamine:

Curr Drug Saf. 2012 Apr;7(2):106-19.

Ketamine induces toxicity in human neurons differentiated from embryonic stem cells via mitochondrial apoptosis pathway.

Bosnjak ZJ, Yan Y, Canfield S, Muravyeva MY, Kikuchi C, Wells CW, Corbett JA, Bai X.

Source

Department of Anesthesiology, The Medical College of Wisconsin, Milwaukee, 53226, USA.

Abstract

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 (ΔΨm), cytochrome c distribution within cells, apoptosis, and ROS production were evaluated. Here we show that ketamine induced ultrastructural abnormalities and dose- and time-dependently caused cell death. In addition, ketamine decreased ΔΨm 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 ΔΨm 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 dose-dependently induces human neurotoxicity at supraclinical concentrations 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.

PMID:

22873495

J Mol Neurosci. 2012 May;47(1):67-75. doi: 10.1007/s12-1. Epub 2011 Dec 8.

Protective function of nicotinamide against ketamine-induced apoptotic neurodegeneration in the infant rat brain.

Ullah N, Ullah I, Lee HY, Naseer MI, Seok PM, Ahmed J, Kim MO.

Source

Department of Biology, College of Natural Sciences-RINS and Applied Life Science-Brain Korea 21, Gyeongsang National University, Chinju 660-701, Republic of Korea.

Abstract

During development, anesthetics activate neuroapoptosis and produce damage in the central nervous system that leads to several types of neurological disorders. A single dose of ketamine (40 mg/kg) during synaptogenesis in a 7-day-old rat brain activated the apoptotic cascade and caused extensive neuronal cell death in the forebrain. In this study, we investigated the protective effect of nicotinamide against ketamine-induced apoptotic neurodegeneration. After 4 h, neuronal cell death induced by ketamine was associated with the induction of Bax, release of cytochrome c into the cytosol, and activation of caspase-3. One single dose of 1 mg/g nicotinamide was administered to a developing rat and was found to inhibit ketamine-induced neuroapoptosis by downregulating Bax, inhibiting

cytochrome c release from mitochondria into cytosol, and inhibiting the expression of activated caspase-3. TUNEL and immunohistochemical analyses showed that ketamine-induced cell death occurred through apoptosis and that it was inhibited by nicotinamide. Fluoro-Jade-B staining demonstrated an increased number of dead cells in the cortex and thalamus after ketamine treatment; treatment with nicotinamide reduced the number of dead cells in these brain regions. Our findings suggest that nicotinamide attenuated ketamine-induced neuronal cell loss in the developing rat brain and is a promising therapeutic and neuroprotective agent for the treatment of neurodevelopmental disorders.

PMID:

22160932

Metab Brain Dis. 2011 Mar;26(1):69-77. doi: 10.1007/s11-1. Epub 2011 Feb 18.

Behavioral changes and mitochondrial dysfunction in a rat model of schizophrenia induced by ketamine.

de Oliveira L, Fraga DB, De Luca RD, Canever L, Ghedim

FV, Matos MP, Streck EL, Quevedo J, Zugno AI.

Source

Laboratory of Neurosciences and National Institute for Translational Medicine (INCT-TM), Postgraduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, 88806-000 Criciúma, SC, Brazil.

Abstract

Evidence from the literature indicates that mitochondrial dysfunction occurs in schizophrenia and other psychiatric disorders. To produce an animal model that simulates psychotic symptoms analogous to those seen in schizophrenic patients, sub-anesthetic doses of N-methyl-D-aspartate (NMDA) receptor antagonists (such as ketamine) have been used. The aim of this study was to evaluate behavioral changes and mitochondrial dysfunction in rats administered ketamine for 7 consecutive days. Behavioral evaluation was performed using an activity monitor 1, 3 and 6 h after the last injection. The activities of mitochondrial respiratory chain complexes I, II, I-III and IV in multiple brain regions (prefrontal cortex, striatum and hippocampus) were also evaluated. Our results showed that hyperlocomotion occurred in the ketamine group 1

and 3 h after the last injection. Stereotypic movements were elevated only when animals were evaluated 1 h after receiving ketamine. In addition, we found that ketamine administration affects the respiratory chain, altering the activity of respiratory chain complexes in the striatum and hippocampus after 1 h, those in the prefrontal cortex and hippocampus after 3 h and those in the prefrontal cortex and striatum 6 h after the last administration of ketamine. These findings suggest that ketamine alters the behavior of rats and changes the activity of respiratory chain complexes in multiple brain regions at different time points.

PMID:

21331561

Br J Anaesth. 2010 Sep;105(3):347-54. doi: 10.1093/bja/aeq169. Epub 2010 Jul 21.

Ketamine induces apoptosis via the mitochondrial pathway in human lymphocytes and neuronal cells.

Braun S, Gaza N, Werdehausen R, Hermanns H, Bauer I, Durieux ME, Hollmann MW, s MF.

Source

Department of Anesthesiology, University of Düsseldorf, Germany.

Abstract

BACKGROUND:

Ketamine has been shown to have neurotoxic properties, when administered neuraxially. The mechanism of this local toxicity is still unknown. Therefore, we investigated the mechanism of cytotoxicity in different human cell lines in vitro.

METHODS:

We incubated the following cell types for 24 h with increasing concentrations of S(+)-ketamine and racemic ketamine: (i) human Jurkat T-lymphoma cells overexpressing the antiapoptotic B-cell lymphoma 2 protein, (ii) cells deficient of caspase-9, caspase-8, or Fas-associated protein with death domain and parental cells, and (iii) neuroblastoma cells (SHEP). N-Methyl-d-aspartate (NMDA) receptors and caspase-3 cleavage were identified by immunoblotting. Cell viability and apoptotic cell death were evaluated flowcytometrically by Annexin V and 7-aminoactinomycin D double staining. Mitochondrial metabolic activity and caspase-3 activation were measured.

RESULTS:

Ketamine, in a concentration-dependent manner, induced apoptosis in lymphocytes and neuroblastoma cell lines. Cell lines with alterations of the mitochondrial pathway of apoptosis were protected against ketamine-induced apoptosis, whereas alterations of the death receptor pathway did not reduce apoptosis. S(+)-Ketamine and racemic ketamine induced the same percentage of cell death in Jurkat cells, whereas in neuroblastoma cells, S(+)-ketamine was slightly less toxic.

CONCLUSIONS:

Ketamine at millimolar concentrations induces apoptosis via the mitochondrial pathway, independent of death receptor signalling. At higher concentrations necrosis is the predominant mechanism. Less toxicity of S(+)-ketamine was observed in neuroblastoma cells, but this difference was minor and therefore unlikely to be mediated via the NMDA receptor.

PMID:

20659914

To: "neurosensorycentersforkids " <neurosensorycentersforkids >; "katyAutismsupport@..." ; "mb12valtrex " <mb12valtrex > Sent: Thursday, January 17, 2013 12:30 PMSubject: Ketamine "Anesthesia"

Hi all,

My child have to do some dental work which requiered ANESTHESIA CALL KETAMINE, has someone use this before?

Any feedback or advise.

Many Thanks