Prolonged inhaled GETA...what's the limit?

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Hamhock

Hamhock

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I have recently been thinking about ventilator and intravenous medication shortages. Inhaled GETA seems to solve many potential problems with both (especially some medication shortages in the NeuroICU). However, I have nearly no knowledge about inhaled general anesthesia.

What are the limits to prolonged inhaled GETA?

What is the longest "case" inhaled GETA that you have experienced?

HH
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Anesth Analg. 2017 Apr;124(4):1190-1199. doi: 10.1213/ANE.0000000000001634.
Safety and Efficacy of Volatile Anesthetic Agents Compared With Standard Intravenous Midazolam/Propofol Sedation in Ventilated Critical Care Patients: A Meta-analysis and Systematic Review of Prospective Trials.
Jerath A1, Panckhurst J, Parotto M, Lightfoot N, Wasowicz M, Ferguson ND, Steel A, Beattie WS.
Author information
1From the *Department of Anesthesia and Pain Medicine, Toronto General Hospital, Toronto, Ontario, Canada; †Department of Anesthesia and Pain Medicine, Middlemore Hospital, Auckland, New Zealand; and ‡Interdepartmental Division of Critical Care, University of Toronto, Ontario, Canada.
Abstract
BACKGROUND:
Inhalation agents are being used in place of intravenous agents to provide sedation in some intensive care units. We performed a systematic review and meta-analysis of prospective randomized controlled trials, which compared the use of volatile agents versus intravenous midazolam or propofol in critical care units.
METHODS:
A search was conducted using MEDLINE (1946-2015), EMBASE (1947-2015), Web of Science index (1900-2015), and Cochrane Central Register of Controlled Trials. Eligible studies included randomized controlled trials comparing inhaled volatile (desflurane, sevoflurane, and isoflurane) sedation to intravenous midazolam or propofol. Primary outcome assessed the effect of volatile-based sedation on extubation times (time between discontinuing sedation and tracheal extubation). Secondary outcomes included time to obey verbal commands, proportion of time spent in target sedation, nausea and vomiting, mortality, length of intensive care unit, and length of hospital stay. Heterogeneity was assessed using the I statistic. Outcomes were assessed using a random or fixed-effects model depending on heterogeneity.
RESULTS:
Eight trials with 523 patients comparing all volatile agents with intravenous midazolam or propofol showed a reduction in extubation times using volatile agents (difference in means, -52.7 minutes; 95% confidence interval [CI], -75.1 to -30.3; P < .00001). Reductions in extubation time were greater when comparing volatiles with midazolam (difference in means, -292.2 minutes; 95% CI, -384.4 to -200.1; P < .00001) than propofol (difference in means, -29.1 minutes; 95% CI, -46.7 to -11.4; P = .001). There was no significant difference in time to obey verbal commands, proportion of time spent in target sedation, adverse events, death, or length of hospital stay.
CONCLUSIONS:
Volatile-based sedation demonstrates a reduction in time to extubation, with no increase in short-term adverse outcomes. Marked study heterogeneity was present, and the results show marked positive publication bias. However, a reduction in extubation time was still evident after statistical correction of publication bias. Larger clinical trials are needed to further evaluate the role of these agents as sedatives for critically ill patients.
PMID: 27828800 DOI: 10.1213/ANE.0000
 
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Eur J Anaesthesiol. 2016 Jan;33(1):6-13. doi: 10.1097/EJA.0000000000000252.
Survival after long-term isoflurane sedation as opposed to intravenous sedation in critically ill surgical patients: Retrospective analysis.
Bellgardt M1, Bomberg H, Herzog-Niescery J, Dasch B, Vogelsang H, Weber TP, Steinfort C, Uhl W, Wagenpfeil S, Volk T, Meiser A.
Author information

Abstract
BACKGROUND:
Isoflurane has shown better control of intensive care sedation than propofol or midazolam and seems to be a useful alternative. However, its effect on survival remains unclear.
OBJECTIVE:
The objective of this study is to compare mortality after sedation with either isoflurane or propofol/midazolam.
DESIGN:
A retrospective analysis of data in a hospital database for a cohort of consecutive patients.
SETTING:
Sixteen-bed interdisciplinary surgical ICU of a German university hospital.
PATIENTS:
Consecutive cohort of 369 critically ill surgical patients defined within the database of the hospital information system. All patients were continuously ventilated and sedated for more than 96 h between 1 January 2005 and 31 December 2010. After excluding 169 patients (93 >79 years old, 10 <40 years old, 46 mixed sedation, 20 lost to follow-up), 200 patients were studied, 72 after isoflurane and 128 after propofol/midazolam.
INTERVENTIONS:
Sedation with isoflurane using the AnaConDa system compared with intravenous sedation with propofol or midazolam.
MAIN OUTCOME MEASURES:
Hospital mortality (primary) and 365-day mortality (secondary) were compared with the Kaplan-Meier analysis and a log-rank test. Adjusted odds ratios (ORs) [with 95% confidence interval (95% CI)] were calculated by logistic regression analyses to determine the risk of death after isoflurane sedation.
RESULTS:
After sedation with isoflurane, the in-hospital mortality and 365-day mortality were significantly lower than after propofol/midazolam sedation: 40 versus 63% (P = 0.005) and 50 versus 70% (P = 0.013), respectively. After adjustment for potential confounders (coronary heart disease, chronic obstructive pulmonary disease, acute renal failure, creatinine, age and Simplified Acute Physiology Score II), patients after isoflurane were at a lower risk of death during their hospital stay (OR 0.35; 95% CI 0.18 to 0.68, P = 0.002) and within the first 365 days (OR 0.41; 95% CI 0.21 to 0.81, P = 0.010).
CONCLUSION:
Compared with propofol/midazolam sedation, long-term sedation with isoflurane seems to be well tolerated in this group of critically ill patients after surgery.
 
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Thanks @BLADEMDA.

Are you able to comment on the economics of prolonged inhaled GETA?

Does anyone have experience with the AnaConDa system? @FFP

HH
 
Hamhock said:
Thanks @BLADEMDA.

Are you able to comment on the economics of prolonged inhaled GETA?

Does anyone have experience with the AnaConDa system? @FFP

HH
Click to expand...


link.springer.com

A technical review of the history, development and performance of the anaesthetic conserving device “AnaConDa” for delivering volatile anaesthetic in intensive and post-operative critical care - Journal of Clinical Monitoring and Computing

There is a shift in critical care to adopt volatile anaesthetics as sedatives for certain patients using mechanical ventilation. Accompanying this shift is a growing body of literature describing the advantages or disadvantages of using isoflurane or sevoflurane for long term sedation. This...
link.springer.com link.springer.com



The AnaConDa reduces drug use and sedation costs by reflecting 90% of it back to the patient while functioning simultaneously as a humidity and moisture exchanger and provides fresh gas flow to the patient. Furthermore, the device is single-use, is of simple construction and is disposable, making any additional post-use maintenance to the ventilators it is used with unnecessary. While the AnaConDa is relatively inexpensive, there is a currently a lack of real, long term data exploring the economics of volatile use; including the device, costs of monitoring, the value of predictable waking and shorter weaning, length of patient ICU and hospital stays, and any additional therapeutic benefits that the volatile drugs may offer.

Should the use of inhaled volatile anaesthetics as ICU sedatives expand, the AnaConDa device seems uniquely poised to provide a simple, safe and cost-effective means of delivering isoflurane and sevoflurane.
 
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BLADEMDA said:
Eur J Anaesthesiol. 2016 Jan;33(1):6-13. doi: 10.1097/EJA.0000000000000252.
Survival after long-term isoflurane sedation as opposed to intravenous sedation in critically ill surgical patients: Retrospective analysis.
Bellgardt M1, Bomberg H, Herzog-Niescery J, Dasch B, Vogelsang H, Weber TP, Steinfort C, Uhl W, Wagenpfeil S, Volk T, Meiser A.
Author information

Abstract
BACKGROUND:
Isoflurane has shown better control of intensive care sedation than propofol or midazolam and seems to be a useful alternative. However, its effect on survival remains unclear.
OBJECTIVE:
The objective of this study is to compare mortality after sedation with either isoflurane or propofol/midazolam.
DESIGN:
A retrospective analysis of data in a hospital database for a cohort of consecutive patients.
SETTING:
Sixteen-bed interdisciplinary surgical ICU of a German university hospital.
PATIENTS:
Consecutive cohort of 369 critically ill surgical patients defined within the database of the hospital information system. All patients were continuously ventilated and sedated for more than 96 h between 1 January 2005 and 31 December 2010. After excluding 169 patients (93 >79 years old, 10 <40 years old, 46 mixed sedation, 20 lost to follow-up), 200 patients were studied, 72 after isoflurane and 128 after propofol/midazolam.
INTERVENTIONS:
Sedation with isoflurane using the AnaConDa system compared with intravenous sedation with propofol or midazolam.
MAIN OUTCOME MEASURES:
Hospital mortality (primary) and 365-day mortality (secondary) were compared with the Kaplan-Meier analysis and a log-rank test. Adjusted odds ratios (ORs) [with 95% confidence interval (95% CI)] were calculated by logistic regression analyses to determine the risk of death after isoflurane sedation.
RESULTS:
After sedation with isoflurane, the in-hospital mortality and 365-day mortality were significantly lower than after propofol/midazolam sedation: 40 versus 63% (P = 0.005) and 50 versus 70% (P = 0.013), respectively. After adjustment for potential confounders (coronary heart disease, chronic obstructive pulmonary disease, acute renal failure, creatinine, age and Simplified Acute Physiology Score II), patients after isoflurane were at a lower risk of death during their hospital stay (OR 0.35; 95% CI 0.18 to 0.68, P = 0.002) and within the first 365 days (OR 0.41; 95% CI 0.21 to 0.81, P = 0.010).
CONCLUSION:
Compared with propofol/midazolam sedation, long-term sedation with isoflurane seems to be well tolerated in this group of critically ill patients after surgery.
Click to expand...
Question is whether we have enough isoflurane. I would hesitate to use sevo for a prolonged time and des drains too fast.
 
If we are discussing inhaled anesthetics on COVID19 patients with ARDS, then we really have zero data on the way the inhaled agents could affect the lungs in these patients.
Common sense suggests that you probably don't want to blast the inflamed pulmonary tissue with irritants like anesthetic vapors.
But even in healthy lungs, no one has studied prolonged exposure to inhaled anesthetics in ICU patients from a morbidity and mortality point of view.
 
Hamhock said:
I have recently been thinking about ventilator and intravenous medication shortages. Inhaled GETA seems to solve many potential problems with both (especially some medication shortages in the NeuroICU). However, I have nearly no knowledge about inhaled general anesthesia.

What are the limits to prolonged inhaled GETA?

What is the longest "case" inhaled GETA that you have experienced?

HH
Click to expand...


You are venturing into the world of unknown. No one knows what volatile anesthetics will do when they interact with covid19. Here's what the ASA/APSF recommended in a recent release:

  • PROVIDING POTENT ANESTHETIC AGENTS (UPDATED APRIL 2, 2020) Anesthesia machines have the capability of providing inhaled anesthetics for sedation during long-term care. While this might be an attractive option if intravenous sedatives are in short supply, it is not generally recommended when the machines are used as ICU ventilators for the following reasons:
    • ● Inhaled anesthetics have profound physiologic effects that can have a significant negative impact on critically ill patients
    • ● Critical care nurses and intensivists are generally not familiar with dosing or monitoring the effects of these drugs
    • ● Scavenging of exhaled gas is required when delivering inhaled anesthetics and may not be readily available outside of the operating room
    • ● High fresh gas flows needed to prevent humidity from accumulating in the circuit will result in high anesthetic consumption and the need to frequently refill the vaporizer. Most of this anesthetic is vented to the atmosphere as waste gas, unabsorbed by the patient.
    • ● Long term sedation with inhaled anesthetics is not a common practice in the United States although it has been used in other countries especially Europe for many years.
      These considerations notwithstanding, if intravenous sedatives need to be rationed, it is possible to sedate patients being ventilated with an anesthesia machine by delivering inhaled anesthetics. Considerations for maximizing the safety and effectiveness of inhaled anesthetics when used for ICU sedation can be found in the document entitled: ASA/APSF Guidance for Use of Volatile Anesthesic for Sedation of ICU Patients
 
Not sure why anyone would try this. IV stuff works very well. I’m not gonna try to reinvent the wheel because the hospital is claiming shortages. Let them find some. It’s their damn job....
 
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dannyboy1 said:
Not sure why anyone would try this. IV stuff works very well. I’m not gonna try to reinvent the wheel because the hospital is claiming shortages. Let them find some. It’s their damn job....
Click to expand...

I am starting to wonder if it's a better choice even when there's plenty of IV agents available.

HH
 
We had a patient in the PICU during my residency who was a terrible case of status epilepticus. The only thing that kept her from seizing was isoflurame-induced coma. She was under an isoflurane anesthetic for ~9 months if I remember. We only knew about the case as anesthesia residents because we would rarely be called at night on call to adjust the iso vaporizer by like 0.1% or so at the direction of the pediatric intensivist.

Don't know the outcome, but I don't imagine it was rosy.
 
B-Bone said:
We had a patient in the PICU during my residency who was a terrible case of status epilepticus. The only thing that kept her from seizing was isoflurame-induced coma. She was under an isoflurane anesthetic for ~9 months if I remember. We only knew about the case as anesthesia residents because we would rarely be called at night on call to adjust the iso vaporizer by like 0.1% or so at the direction of the pediatric intensivist.

Don't know the outcome, but I don't imagine it was rosy.
Click to expand...

WTF... 9 months? How old was this kid? Was there some sort of plan involved in this?
 
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Hamhock said:
I am starting to wonder if it's a better choice even when there's plenty of IV agents available.
Click to expand...
I don't know. I'm skeptical. I can't help but feel like this guy could tell us something about the effects of prolonged exposure to mind altering inhaled organic solvents.

0721051gold1.jpg

I mean, that stuff melts plastic. It's got to be bad for us.
 
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pgg said:
I don't know. I'm skeptical. I can't help but feel like this guy could tell us something about the effects of prolonged exposure to mind altering inhaled organic solvents.

0721051gold1.jpg

I mean, that stuff melts plastic. It's got to be bad for us.
Click to expand...

Yeah, I remain skeptical too -- but not so much that I am going to stop investigating just yet. I don't know the effects of prolonged exposure to the inhaled agents, but I do know the effects of prolonged exposure to versed infusions.

As a tangential: I am disappointed that many of the inhaled vs IV studies in the AnaConDa trials used midazolam as a "control". Hell, I bet I could show you sublingual cocaine would be better than prolonged exposure to high-dose versed.

I'd really like to see a comparison between prolonged inhaled agents and more modern sedatives/analgesics in the ICU. [Edit: I just googled to satisfy by curiosity and both propofol and versed seem to come from the 1970s...but I think my point still stands.]

HH
 
pgg said:
I don't know. I'm skeptical. I can't help but feel like this guy could tell us something about the effects of prolonged exposure to mind altering inhaled organic solvents.

0721051gold1.jpg

I mean, that stuff melts plastic. It's got to be bad for us.
Click to expand...
Are we supposed to understand the picture? I don't get it.
 
pgg said:
He's famous for his many mugshots. Usually gold or silver paint. Apparently the metallic colors have more toluene or xylene in them than non-metallic, making the high from huffing them stronger.
Click to expand...

also a very common meme/callback in Fark photoshop threads. Although, there, I think we’re supposed to believe it’s moustard.
 
B-Bone said:
We had a patient in the PICU during my residency who was a terrible case of status epilepticus. The only thing that kept her from seizing was isoflurame-induced coma. She was under an isoflurane anesthetic for ~9 months if I remember. We only knew about the case as anesthesia residents because we would rarely be called at night on call to adjust the iso vaporizer by like 0.1% or so at the direction of the pediatric intensivist.

Don't know the outcome, but I don't imagine it was rosy.
Click to expand...
They seriously kept a kid in the PICU for nine months under GA?

What the hell was the long term plan? Go home in an Isolflurane Coma with an anesthesia machine? And never wake up because that leads to status? Because that seems like a life well lived.

What a total waste of resources.
 
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FYI volatiles are horrible for the environment. If you’re talking about theoretically switching over to them long term for all patients it warrants consideration.
 
I think in the future we will have volatiles used for ICU sedation, but only with an effective scavenging system, and a way to use them with an ICU vent like above.

There is some suggestion that they are anti inflammatory, hence lots of studies trying tk show some difference between volatiles and TIVA for all these cancer surgeries. I doubt they would “interact” in any way with covid19. There is good evidence that volatiles are protective against ischemia, more so than IV anesthetics line propofol.

As an aside, the american heart association recommends volatiles for all patients getting GA with CAD because there is some studies suggesting less troponin rise and myocardial injury after bypass cases.
 
If xenon ever becomes (much, much, much) cheaper and alfaxalone pans out as the ideal IV anesthetic, those will probably eventually become some of the more standard ICU sedation meds.
 
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