Remimidazolam

[BLADEMDA]

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The study mentioned here has some major clinical issues.

1. The dosage used was fairly high
2. Bradycadia is a known side-effect so I would not want the drug on board for cases known to cause bradycardia (like insufflation, carotid manipulation ,etc).
3. Discharge times will be longer if the infusion is not turned off at least 30 minutes prior to the end of the case


The reason for stopping the trial was severe bradycardia in five patients associated with asystole for three of them in the dexmedetomidine group. All of these bradycardias happened before the reduction of dexmedetomidine doses decided on December 28, 2018. None of these bradycardias/asystoles led to postoperative complications or sequelae. 3 of these asystoles occurred when the surgeon requested insufflation of the abdomen while the Dex was on board.

If you use Dex/Precedex regularly then you know severe bradycardia is a concern especially with bolus doses. The onset of the drug takes 5-10 minutes but if you push it IV upfront (1 ug/kg) you will get severe bradycardia +/- severe hypertension. A better way is to do a single bolus dose of 1 ug/kg over 10 minutes prior to the start of surgery. Clinically, I find that for short cases of 45 minutes or less all I need is just a single bolus dose. Otherwise, discharge time in the PACU may be significantly prolonged.

 

[BLADEMDA]

Here is why I use Precedex from time to time on both inpatients and outpatients:

Further, significantly more patients did not need any opioid administration within the 48 h after surgery in the balanced opioid-free anesthesia with dexmedetomidine group. They also experienced less postoperative nausea and vomiting. One can hypothesize that morphine sparing might not be the only reason for the reduction of postoperative nausea and vomiting. Dexmedetomidine could have a prolonged antiemetic effect, as previously suggested.2

This drug requires a good understanding of pharmikokinetics and pharmokodynamics prior to using it. By no means is Precedex without many clinical issues but in the right hands I found it to be a very effective, useful drug in my practice.

 

[Airway]

1. The dosage used was fairly high
2. Bradycadia is a known side-effect so I would not want the drug on board for cases known to cause bradycardia (like insufflation, carotid manipulation ,etc).
3. Discharge times will be longer if the infusion is not turned off at least 30 minutes prior to the end of the case

Agree agree agree But the benefit of precedex should outweigh these issues. Imo the data (other papers) don't show decrease in 24-hour and long-term opiod consumption nor do they decrease delirium rates outside of cardiac surgery...

 

[BLADEMDA]

Agree agree agree But the benefit of precedex should outweigh these issues. Imo the data (other papers) don't show decrease in 24-hour and long-term opiod consumption nor do they decrease delirium rates outside of cardiac surgery...

I think delirium rates are lower with Precedex than with most other agents except perhaps Propofol. That is my experience with using it on many patients with memory loss.

 

[BLADEMDA]

Dexmedetomidine for prevention of delirium in elderly patients after non-cardiac surgery: a randomised, double-blind, placebo-controlled trial - PubMed

Braun Anaesthesia Scientific Research Fund and Wu Jieping Medical Foundation, Beijing, China. Study drugs were manufactured and supplied by Jiangsu Hengrui Medicine Co, Ltd, Jiangsu, China.

pubmed.ncbi.nlm.nih.gov

Low-Dose Nocturnal Dexmedetomidine Prevents ICU Delirium. A Randomized, Placebo-controlled Trial - PubMed

Nocturnal administration of low-dose dexmedetomidine in critically ill adults reduces the incidence of delirium during the ICU stay; patient-reported sleep quality appears unchanged. Clinical trial registered with www.clinicaltrials.gov (NCT01791296).

pubmed.ncbi.nlm.nih.gov

The effect of dexmedetomidine on delirium and agitation in patients in intensive care: systematic review and meta-analysis with trial sequential analysis - PubMed

Delirium is common in intensive care patients. Dexmedetomidine is increasingly used for sedation in this setting, but its effect on delirium remains unclear. The primary aim of this review was to examine whether dexmedetomidine reduces the incidence of delirium and agitation in intensive care...

pubmed.ncbi.nlm.nih.gov

 

[DrOwnage]

I personally would be ok with a colonoscopy under Midaz and fentanyl. But if it’s an EGD give me that prop. I had an EGD when I was 16 and still remember 5 people standing around me, looking into my mouth with the scope while I was gagging on it. I get a lot of patients who have had bad prior experiences with conscious sedation. The stimulation of an EGD is just much more than a colonoscopy. Usually takes those patients 25 minutes to wake up in PACU if they were comfortable during the case with conscious sedation. I’m of the mindset that just because someone won’t remember it, it doesn’t make it ok to have them struggle and suffer.

 

[Airway]

@BLADEMDA
Gold standard paper:. https://www.nejm.org/doi/full/10.1056/NEJMoa2024922

 

[vector2]

@BLADEMDA
Gold standard paper:. https://www.nejm.org/doi/full/10.1056/NEJMoa2024922

Indeed, we quote this paper all the time in the ICU....with the caveat

"214 patients received dexmedetomidine at a median dose of 0.27 μg per kilogram per hour, and 208 received propofol at a median dose of 10.21 μg per kilogram per minute. The median duration of receipt of the trial drugs was 3.0 days (interquartile range, 2.0 to 6.0), and the median RASS score was −2.0 (interquartile range, −3.0 to −1.0)."


The medians were essentially homeopathic doses for both drugs.

 

[nimbus]

Indeed, we quote this paper all the time in the ICU....with the caveat

"214 patients received dexmedetomidine at a median dose of 0.27 μg per kilogram per hour, and 208 received propofol at a median dose of 10.21 μg per kilogram per minute. The median duration of receipt of the trial drugs was 3.0 days (interquartile range, 2.0 to 6.0), and the median RASS score was −2.0 (interquartile range, −3.0 to −1.0)."


The medians were essentially homeopathic doses for both drugs.

Seriously I think I’d still be pretty good at solving jumble and sudoku on those doses.

 

[epidural man]

Doesn’t matter.

None of us will have a job once someone figures out the right cyclodextrine to put alfaxalone in.

Not sure what happened to Phaxan.

Pharmacokinetic and Pharmacodynamic Analysis of Alfaxalone... : Anesthesia & Analgesia

(PK) and pharmacodynamic (PD) characteristics of alfaxalone given as a bolus intravenous injection of this formulation to human male volunteers. METHODS: A dose of 0.5 mg/kg (0.42–0.55 mg/kg) of alfaxalone [mean (range)] was given by single intravenous bolus injection to 12 healthy subjects...

journals.lww.com

 

[Airway]

Indeed, we quote this paper all the time in the ICU....with the caveat

"214 patients received dexmedetomidine at a median dose of 0.27 μg per kilogram per hour, and 208 received propofol at a median dose of 10.21 μg per kilogram per minute. The median duration of receipt of the trial drugs was 3.0 days (interquartile range, 2.0 to 6.0), and the median RASS score was −2.0 (interquartile range, −3.0 to −1.0)."


The medians were essentially homeopathic doses for both drugs.

Respectfully disagree (re homeopathic). Coma and deeply sedated were > 30% in each group. More then 90% were -1 or more deeply sedated. The median dose of fentanyl was 60ish mcg/hr. It's Wonderful if you can get nursing to go along with light sedation... These institutions had good nursing and aggressive sat work. (I feel like I work at a rass goal of coma institution now). No one seems to notice that the patient has moved one inch in two weeks. Ugh

 

[BLADEMDA]

What I can tell you all is that I encounter very elderly patients with memory loss and dementia routinely. I prefer to avoid midazolam and use light doses of propofol combined with regional techniques. If I need To add an agent besides propofol precedex is a good option. IMHO, both of those drugs in moderate doses are the best we have currently for those types of patients.

sure, I know what the literature says and I’ve read the studies but I also actually practice in the real world on a lot of elderly patients and they seem to do better With those drugs in terms of delirium and postop confusion.

So, I’m skeptical Remi midazolam will be a better choice for this subgroup than propofol. I can personally state that my family members and myself were grateful to receive propofol for our Gi procedures. Propofol is like flying first class while midazolam is like flying Coach to Europe. Both will get you there but which would you prefer?

While I accept the article about precedex from the NEJM I would not dismiss the other articles showing a benefit from precedex. At low doses Both drugs may be equivalent but at higher doses like we use in the OR there may be a benefit by combining them to decrease postoperative delirium and confusion. IMHO, I believe that benefit is real and relevant to our practice.

 

[BLADEMDA]

CONCLUSION​

Adding peri-operative dexmedetomidine to a total intravenous anaesthetic safely reduces POD and emergence agitation in elderly patients undergoing open transthoracic oesophagectomy. These benefits were associated with a postoperative reduction in circulating levels of the pro-inflammatory cytokine IL-6 and stabilisation of the haemodynamic profile.

Dexmedetomidine for prevention of postoperative delirium in ... : European Journal of Anaesthesiology | EJA

rce. OBJECTIVE To investigate the efficacy and safety of dexmedetomidine in reducing POD in elderly patients after transthoracic oesophagectomy with total intravenous anaesthesia (TIVA). DESIGN A randomised, double-blind, placebo-controlled trial. SETTING Single-centre, tertiary care...

journals.lww.com

Dexmedetomidine reduces the incidence of postoperative delirium after cardiac surgery: a meta-analysis of randomized controlled trials - BMC Anesthesiology

Background The role of dexmedetomidine in preventing postoperative delirium (POD) after cardiac surgery remains controversial because of several recent trials with negative results. We aimed to perform an updated meta-analysis of randomized controlled trials (RCTs) to clarify this controversy...

bmcanesthesiol.biomedcentral.com

Editor’s key points
Postoperative delirium is common, particularly in elderly patients, and is associated with worse outcomes.
In this meta-analysis of randomised trials of dexmede- tomidine in adult surgical patients, dexmedetomidine use significantly reduced the incidence of postoperative delirium.
Efficacy was similar for younger and older adults, and for intra- or post-operative administration.

DEFINE_ME

 

[vector2]

Respectfully disagree (re homeopathic). Coma and deeply sedated were > 30% in each group. More then 90% were -1 or more deeply sedated. The median dose of fentanyl was 60ish mcg/hr. It's Wonderful if you can get nursing to go along with light sedation... These institutions had good nursing and aggressive sat work. (I feel like I work at a rass goal of coma institution now). No one seems to notice that the patient has moved one inch in two weeks. Ugh

Don't you agree there's some discordance going on there if the dex group had a median dose of 0.2 mcg/kg/hr but yet 38% in that group were RASS -5 or -4 and another 14% were RASS -3?

That tells me that there must be some kind of conflating clinical effect be it from other medications (benzos, opioids, antipsychotics etc) or some abnormally severe degree of illness / high degree of baseline neurological insult, because that dose is indeed homeopathic in a pt who is intubated on mechanical ventilation. IMO, this study better highlights the importance of multimodal analgosedation than it does the equivalence of dex and prop.

Say you're doing a pain relief study comparing tylenol and ibuprofen. Group A gets median dose 10 mg of tylenol. Group B gets median dose 10 mg of ibuprofen. Both groups get 120 mg of oxycodone IR. Can one claim that tylenol and ibuprofen are equivalent since both groups had equivalent pain relief and adverse events?

 

[Airway]

IMO, this study better highlights the importance of multimodal analgosedation than it does the equivalence of dex and prop.

Agree. I may have attended at one of these institutions at some point. The sick people were in comas with or without drugs... And I also think that it speaks further to the nihilism of what we do. I thought this study might show something because of mechanistic thinking/hopefulness (as @BLADEMDA quoted re il6).

I suspect the way to go (to show benefit/positive signal) is an ERAS like protocol and then a composite outcome.

A good reminder:

Which Multicenter Randomized Controlled Trials in Critical Care Medicine Have Shown Reduced Mortality? A Systematic Review - PubMed

A systematic literature search provided no conclusive evidence of any pharmacologic intervention that has consistently reduced mortality in critically ill patients. Strategies associated with improved or noninvasive mechanical ventilation were associated with reduced mortality.

pubmed.ncbi.nlm.nih.gov

 

[FiO2@21]

Small precedex doses go a long way.. 0.25 mcg/kg given 20-30 min prior to wake up doesn't seem to slow down my wake ups when I choose to use it. 1/4 of those patients are frequently talking and on room air prior to exit from OR.

But most patients don't need it. I give it for carotids, thyroids, super painful surgeries, super anxious patients.

And for the ones who everyone agrees would benefit from waking up 30 min from now in PACU... they get more than 0.25.