Feb 10, 2019
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As a nursing student, during one of our rotations I noticed that a lot of stage 4 cancer patients/ terminally ill patients were sedated with anesthetics such as midazolam or propofol and they referred to it as "paliative sedation." We were told that the two most common reasons for the sedation are due to persistent/ treatment resistant pain or nausea/vomiting.

I understand how sedation can help the pain because you cannot feel pain if you are asleep, but how does it help with nausea/vomiting? People can still vomit in their sleep as we often see with people who are overly intoxicated. Wouldn't being sedated just put them at risk for aspiration?
 

Frazier

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As a nursing student, during one of our rotations I noticed that a lot of stage 4 cancer patients/ terminally ill patients were sedated with anesthetics such as midazolam or propofol and they referred to it as "paliative sedation." We were told that the two most common reasons for the sedation are due to persistent/ treatment resistant pain or nausea/vomiting.

I understand how sedation can help the pain because you cannot feel pain if you are asleep, but how does it help with nausea/vomiting? People can still vomit in their sleep as we often see with people who are overly intoxicated. Wouldn't being sedated just put them at risk for aspiration?
Great question. It's fantastic to see your interest and you starting early to think not just about symptom management, but also patient safety.

The topic of benzo, propofol, etc sedation has been explored in recent decades. Much goes into the decision and hopefully efforts trialed and exhausted leading up to that point. You can check out a short and sweet article about sedation and refractory nausea below:


If you read that article, takes under 10 minutes, you will have a pretty good foundation to answer your question -- and also for you to answer when a student asks you the same thing on the ward in a few years! :)
 
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Feb 10, 2019
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Great question. It's fantastic to see your interest and you starting early to think not just about symptom management, but also patient safety.

The topic of benzo, propofol, etc sedation has been explored in recent decades. Much goes into the decision and hopefully efforts trialed and exhausted leading up to that point. You can check out a short and sweet article about sedation and refractory nausea below:


If you read that article, takes under 10 minutes, you will have a pretty good foundation to answer your question -- and also for you to answer when a student asks you the same thing on the ward in a few years! :)
Thank you for the reply! I actually read this article which prompted me to ask this question here haha. So despite if the particular sedative being used has anti emetic properties or not, I saw and read how the sedation itself can terninate a refractory vomiting episode that doesn't respond to antiemetics. For instance, I see that this is sometimes done for patients with cyclic vomiting syndrome who have a persistent/ relentless episode that doesn't respond to antiemetics.

So my question is how does this work and how does being sedated stop vomiting? I read somewhere that by being asleep, it shuts of the vomiting center in the brain. But as we sometimes see, people under anesthesia or who are really intoxicated and unconscious can still vomit during sleep and risk aspirating. So how is it that sedation works to stop vomiting then?
 

Frazier

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Thank you for the reply! I actually read this article which prompted me to ask this question here haha. So despite if the particular sedative being used has anti emetic properties or not, I saw and read how the sedation itself can terninate a refractory vomiting episode that doesn't respond to antiemetics. For instance, I see that this is sometimes done for patients with cyclic vomiting syndrome who have a persistent/ relentless episode that doesn't respond to antiemetics.
So my question is how does this work and how does being sedated stop vomiting? I read somewhere that by being asleep, it shuts of the vomiting center in the brain. But as we sometimes see, people under anesthesia or who are really intoxicated and unconscious can still vomit during sleep and risk aspirating. So how is it that sedation works to stop vomiting then?
Awesome! So we dig down a little deeper into mechanisms like you allude to above, and we see that majority of all this is theoretically based on what we know about N&V (like you mention vomit center, etc.), what we know about the drugs, and trial results of how these drugs improve XYZ symptoms (e.g. nausea)... then fill in the gaps with theory ("XYZ med improves nausea when given to patients likely via this pathway").

Let's flip back to more of the literature, with now a look at specific points addressing the drugs you mentioned:

In order to understand the pathophysiology underlying nausea, it is important to introduce the concept of the dynamic threshold [Stern, 2002]. It is proposed that each individual has a threshold for nausea that changes minute by minute. At any given moment, the threshold depends on the interaction of certain inherent factors of the individual with the more changeable psychological states of anxiety, anticipation, expectation and adaptation [Stern, 2002]. This dynamic interaction likely explains the inter- and intra-individual variability that is typically encountered in the face of a nauseogenic stimulus [Stern, 2002]. Stimuli giving rise to nausea and vomiting originate from visceral, vestibular, and chemoreceptor trigger zone inputs which are mediated by serotonin/dopamine, histamine/acetylcholine and serotonin/dopamine, respectively.
In regards to benzo sedation:
It is postulated that the antiemetic mechanism of action involves dopamine in the chemoreceptor trigger zone [Di Florio and Goucke, 1993; Takada et al. 1993; Rodola, 2006]. Its primary mode of action is via its sedative, anxiolytic, and amnestic properties in reducing the anticipatory component of nausea [Cooper and Gent, 2002; Chepyala and Olden, 2008].
In regards to propofol:
Although the precise mechanism of propofol's antiemetic effect has not been elucidated, several mechanisms have been proposed, including a direct depressant effect on the CTZ, the vagal nuclei, and other centers implicated in PONV. In animal models, propofol has been shown to decrease synaptic nerve transmission in the olfactory cortex[67] and to decrease serotonin levels in the area postrema.
So, as you suspected, there is indeed the theoretical basis of mechanism on paper lined with the witnessed efficacy in practice on living, breathing patients. As unsatisfying as it might be, the answers aren't 100% there yet.

You make an important point which is also worth revisiting: if we are sedating these folks, isn't that increasing risk of aspiration? I imagine it might depend on who you ask. I feel it is "yes and no". You are right, a person that is not intubated, that vomits while sedated to whatever RASS is less likely to protect their airway to the extent they would without any sedatives on board -- therefore there is increased risk of aspiration in a sedated patient that vomits.

However, the sedation in this matter is itself being administered to stop the vomiting to begin with... as you read above, there is a large sensory and psychological component to N&V. Being sedated (theoretically) tackles the issue from that angle. Also, as you know, these palliative patients are often very sick and weak, perhaps with dementia, and not protecting their airway well at baseline. With refractory N&V in these patients, it is just a waiting game until they aspirate, this is of course ignoring the elephant in the room of suffering the actual sensation of nausea and corresponding decrease in QoL when it becomes refractory (huge focus of palliative care, right?). So, if the patient does not get satisfactory relief with first line, second line, third line, XYZ line medication approaches, then comes the option for what you described "palliative sedation" with drugs such as benzos, propofol which work theoretically via the mechanisms we discussed a couple paragraphs up, for the reasons we discussed a few sentences up. Sedation, in a vacuum, increases risk of aspiration when vomiting is inevitable; however, the regimens we are discussing are to hopefully prevent the vomiting and, therefore, the aspirating to begin with. It always circles back to benefit vs risk.

Good review:
 
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Feb 10, 2019
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Awesome! So we dig down a little deeper into mechanisms like you allude to above, and we see that majority of all this is theoretically based on what we know about N&V (like you mention vomit center, etc.), what we know about the drugs, and trial results of how these drugs improve XYZ symptoms (e.g. nausea)... then fill in the gaps with theory ("XYZ med improves nausea when given to patients likely via this pathway").

Let's flip back to more of the literature, with now a look at specific points addressing the drugs you mentioned:



In regards to benzo sedation:


In regards to propofol:


So, as you suspected, there is indeed the theoretical basis of mechanism on paper lined with the witnessed efficacy in practice on living, breathing patients. As unsatisfying as it might be, the answers aren't 100% there yet.

You make an important point which is also worth revisiting: if we are sedating these folks, isn't that increasing risk of aspiration? I imagine it might depend on who you ask. I feel it is "yes and no". You are right, a person that is not intubated, that vomits while sedated to whatever RASS is less likely to protect their airway to the extent they would without any sedatives on board -- therefore there is increased risk of aspiration in a sedated patient that vomits.

However, the sedation in this matter is itself being administered to stop the vomiting to begin with... as you read above, there is a large sensory and psychological component to N&V. Being sedated (theoretically) tackles the issue from that angle. Also, as you know, these palliative patients are often very sick and weak, perhaps with dementia, and not protecting their airway well at baseline. With refractory N&V in these patients, it is just a waiting game until they aspirate, this is of course ignoring the elephant in the room of suffering the actual sensation of nausea and corresponding decrease in QoL when it becomes refractory (huge focus of palliative care, right?). So, if the patient does not get satisfactory relief with first line, second line, third line, XYZ line medication approaches, then comes the option for what you described "palliative sedation" with drugs such as benzos, propofol which work theoretically via the mechanisms we discussed a couple paragraphs up, for the reasons we discussed a few sentences up. Sedation, in a vacuum, increases risk of aspiration when vomiting is inevitable; however, the regimens we are discussing are to hopefully prevent the vomiting and, therefore, the aspirating to begin with. It always circles back to benefit vs risk.

Good review:
Thank you so much! I appreciate this. So basically the degree or level of sedation also plays a role. So for example, if a person is only moderately sedated, their vomiting center might not be supressed and therefore can still vomit, however they are out of it enough where their gag reflex is lagging and can't respond to the vomiting and risk aspirating. However if they are more deeply sedated/ anesthetized it is enough to shut down their vomiting center/ vomiting reflex as well, eliminating the vomiting and therefore the risk of aspiration.
 

Frazier

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Thank you so much! I appreciate this. So basically the degree or level of sedation also plays a role. So for example, if a person is only moderately sedated, their vomiting center might not be supressed and therefore can still vomit, however they are out of it enough where their gag reflex is lagging and can't respond to the vomiting and risk aspirating. However if they are more deeply sedated/ anesthetized it is enough to shut down their vomiting center/ vomiting reflex as well, eliminating the vomiting and therefore the risk of aspiration.
No problem. I agree the level of sedation plays a role in the concepts we discussed earlier. Although, I think the goal rests more in conquering refractory nausea sensations with a consequential reduction of the likelihood of precipitated emesis (versus trying to eliminate gag reflex). I agree eliminating the vomiting decreases risk of aspiration. :thumbup:
 
Feb 10, 2019
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No problem. I agree the level of sedation plays a role in the concepts we discussed earlier. Although, I think the goal rests more in conquering refractory nausea sensations with a consequential reduction of the likelihood of precipitated emesis (versus trying to eliminate gag reflex). I agree eliminating the vomiting decreases risk of aspiration. :thumbup:
So would this same principle of sedation work for relentless vomiting due to lets say gastric cancer or gastroenteritis since the triggering nausea signal into the vomiting center of the brain stem is originating in the body as opposed to the brain?
 
Feb 10, 2019
49
2
1
No problem. I agree the level of sedation plays a role in the concepts we discussed earlier. Although, I think the goal rests more in conquering refractory nausea sensations with a consequential reduction of the likelihood of precipitated emesis (versus trying to eliminate gag reflex). I agree eliminating the vomiting decreases risk of aspiration. :thumbup:
Let me ask this a better way, what level of sedation is required to supress intractable vomiting?
 

Frazier

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The level of sedation will depend on the patient, the severity of their sxs, etc.

RASS between -2 to -4 is typical. Aim is to utilize least amount of sedation to reach target outcome. In other words, if -2 gets the job done then no need to go further to -3. How much of X drug to reach RASS -2 versus -4 depends on the patient, their tolerance, size, metabolism, etc.

Protocols vary across facilities and institutions; however, below is some good info from one facility which elaborates on more of these issues :)