I have a question on the relative uselessness of dexmedetomidine for ethanol withdrawal that you guys alluded to. When you say that dex masks the vital signs, do you mean that it isn't *really* reducing sympathetic tone? I know that dex (or clonidine) won't reduce seizure episodes alone, but aren't the labile blood pressures and crazy sustained tachycardia what really kills people? I always thought a big goal of GABA agonism or NMDA antagonism was to reduce the massive sympathetic surge as well as the seizures, and seems like dex would achieve at least part of that goal, just a little further down in the pathway.
Thanks for the comments. I think the key with dexmedetomidine is that it doesn't replace the other sedative agents we would be giving (benzodiazepines, barbiturates, potentially ketamine and/or propofol). I deep dive this topic on the ALiEM site: https://www.aliem.com/2013/02/dexmedetomidine-precedex-as-adjunct-for/. Dr. Lewis Nelson and I co-authored a letter to the editor about one of the dexmedetomidine studies that also discusses some of the issues: https://www.ncbi.nlm.nih.gov/pubmed/27139007. If you need an electronic copy, feel free to email me at bryanhayes13@gmail.com. It's not that dex doesn't decrease sympathetic tone, it's more that, by itself, it doesn't treat the underlying pathophysiology of ethanol withdrawal (at least from what we currently understand).
Okay, but let me ask this. Our source of the problem is in the brain. Where the problem expresses itself is waaaaay downstream, in the cardiovascular system (what really kills people). Why does it matter to stop the crazy vital signs higher up in the brain instead of further downstream (sympathetic output)?
Put another way, isn't the he major problem is GABA receptor downregulation? If so, do benzos actually increase the speed of upregulation of the receptors, or just flog more out of the ones that are left? Would dex allow you to upregulate your GABA receptors more rapidly? Sorry for all the random questions.
Whit F. - January 4, 2019 4:36 AM
Hey guys. Great segment.
I have a question on the relative uselessness of dexmedetomidine for ethanol withdrawal that you guys alluded to. When you say that dex masks the vital signs, do you mean that it isn't *really* reducing sympathetic tone? I know that dex (or clonidine) won't reduce seizure episodes alone, but aren't the labile blood pressures and crazy sustained tachycardia what really kills people? I always thought a big goal of GABA agonism or NMDA antagonism was to reduce the massive sympathetic surge as well as the seizures, and seems like dex would achieve at least part of that goal, just a little further down in the pathway.
Bryan H. - January 4, 2019 6:32 AM
Thanks for the comments. I think the key with dexmedetomidine is that it doesn't replace the other sedative agents we would be giving (benzodiazepines, barbiturates, potentially ketamine and/or propofol). I deep dive this topic on the ALiEM site: https://www.aliem.com/2013/02/dexmedetomidine-precedex-as-adjunct-for/. Dr. Lewis Nelson and I co-authored a letter to the editor about one of the dexmedetomidine studies that also discusses some of the issues: https://www.ncbi.nlm.nih.gov/pubmed/27139007. If you need an electronic copy, feel free to email me at bryanhayes13@gmail.com. It's not that dex doesn't decrease sympathetic tone, it's more that, by itself, it doesn't treat the underlying pathophysiology of ethanol withdrawal (at least from what we currently understand).
Whit F. - January 23, 2019 11:52 AM
Okay, but let me ask this. Our source of the problem is in the brain. Where the problem expresses itself is waaaaay downstream, in the cardiovascular system (what really kills people). Why does it matter to stop the crazy vital signs higher up in the brain instead of further downstream (sympathetic output)?
Put another way, isn't the he major problem is GABA receptor downregulation? If so, do benzos actually increase the speed of upregulation of the receptors, or just flog more out of the ones that are left? Would dex allow you to upregulate your GABA receptors more rapidly? Sorry for all the random questions.
Whit F. - January 23, 2019 11:54 AM
Oh wait. Just read that GABA depletion causes the problem, not receptor downregulation. Never mind.