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Intractable Nausea and Vomiting: Gordon J. Wood, MD, discusses the management of intractable nausea and vomiting in patients at the end of life.
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Intractable Nausea and Vomiting: Gordon J. Wood, MD, discusses the management of intractable nausea and vomiting in patients at the end of life.
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>> I'm Joan Stephenson, editor of JAMA's Medical News and Perspectives Section. Today, I have the pleasure of speaking with Dr. Gordon J. Wood about managing intractable nausea and vomiting in patients at the end of life, which is a topic in Care at the Close of Life discussed in a chapter co-written by today's guest expert. Dr. Wood, why don't you introduce yourself to our listeners? >> Thank you for having me. My name is Gordon Wood. I am the director of Palliative Medicine and Supportive Care at Northwestern Lake Forest Hospital in Lake Forest, Illinois.
I also attend on the in-patient palliative care consult service at Northwestern Memorial Hospital in downtown Chicago. Additionally, I'm an associate medical director at Midwest Palliative and Hospice Care Center in Glenview, Illinois. >> Dr. Wood, I know that nausea and vomiting are very common symptoms at the end of life. What is meant by intractable nausea and vomiting, and what type of patients are at risk for it? >> Well, the formal definition that we use for intractable nausea and vomiting is nausea and vomiting that's not adequately controlled after multiple anti-emetics are used in series and/or in combination.
Practically speaking, though, I use the same sort of mechanism-based approach for every patient near the end of life who is bothered by nausea and vomiting. What I mean by mechanism-based approach is sort of a three-step approach. First step is doing a thorough evaluation to determine the cause of the nausea. The second step is using knowledge of pathophysiology to determine the receptors involved. And finally, the third step is choosing anti-emetics which block those receptors. Unfortunately, I get to use this, you know, frequently because a lot of patients near the end of life develop nausea and vomiting.
Some of the more common scenarios are patients requiring opioids for pain control. A lot of patients tolerate these well, but some patients have very severe symptoms of nausea and vomiting. Sometimes patients receiving chemotherapy or radiation, especially if the radiation is to the GI tract, patients with brain tumors, and the really tough ones seem to be patients with altered anatomy. And that could be from a malignant bowel obstruction or from things we do to them, like gastroesophageal stents or other surgical or interventional alterations of the anatomy.
>> So what are the first steps that clinicians should take to evaluate nausea and vomiting in patients at the end of life? And also, can you describe some examples of clues that clinicians can look for to determine the cause? >> Well, what I really try to do is take a really systematic approach, and I do a head-to-toe approach, and I think it works really well. And what I mean by head-to-toe approach is I sort of start at the top and for each part of the body I try to think of the causes of nausea and vomiting that could come from that part of the body, and that helps direct my questions and my history and also what I do in my physical exam.
So just sort of going through this briefly, I start with the brain at the top, and the causes there are increased intracranial pressure or meningeal irritation, anxiety, and any of the five senses. So I ask about things like headache or whether the patient feels nausea come on while they're driving to their chemotherapy session. Next down in the head-to-toe approach is the ears. I think about the vestibular system and motion-induced nausea or labyrinth disorders, so I'm asking about vertigo. I'm looking for a nystagmus on my exam.
Next down is the nose, so I ask about post-nasal drip. And then next down is the mouth, so I look for thrush or herpes. And then next down is the esophagus, so I ask about symptoms of GERD. Next down is the abdomen, and there's lots of causes here; gastritis, peptic ulcer disease, stasis, bowel obstruction, gallbladder, liver, pancreatic disease, bowel compression by a large spleen, GI radiation. I try to ask about all of these types of symptoms and ask about it in my history and then examine for them on my exam.
For example, one of the things we try to do is get people to characterize their nausea. If they describe nausea that is a large volume and happens infrequently or the vomiting happens infrequent and when they throw up, it relieves the sense of nausea that can be a sign of a malignant bowel obstruction or a partial bowel obstruction. Next down on the head to toe is the rectum. That makes me think of constipation. I ask about that in detail, and I do a rectal exam. And then once you've gone sort of from the brain all the way down to the rectum, you think about systemic causes that are throughout the whole body, so these are medications like opioids, antidepressants, antibiotics, chemotherapy, endocrine causes like adrenal insufficiency, electrolytes and other metabolic issues like hyponatremia, hypercalcemia, renal failure, liver failure, bacterial toxins, and then ask about these.
So did they just start a new antidepressant and maybe that's why they're nauseous, or did they just stop a steroid and maybe their adrenally insufficient. So this sort of head-to-toe approach I think is the key way that I approach the evaluation of a patient with nausea and vomiting. >> Dr. Wood, you started at the head in your evaluation, and that leads to the question, what role does the brain play in intractable nausea and vomiting? And why is it important for clinicians to understand which neural pathways may be responsible for a patient's symptoms?
>> Well, the brain is key because that's where all of the signals from all of those head-to-toe causes get integrated. If there are enough signals, the brain triggers the nausea and vomiting reflex. So understanding the neural pathways allows you to determine which pathways are involved in a particular patient's nausea. And then you can choose an antiemetic to block the receptors in that pathway. So there are four main pathways that all come together in the vomiting center. And the vomiting center is located in the brain stem, and the key receptors in the vomiting center are acetylcholine, histamine type 1 and 5-HT2.
So the first of the four pathways is what we call the cortex. And the cortex has direct afferents into the vomiting center. And this mediates nausea due to sensory input, anxiety, meningeal irritation and increased intracranial pressure. The second main pathway is the vestibular system. And this mediates vomiting via the vestibulocochlear nerve using main receptors acetylcholine and histamine type one. And this is responsible for nausea due to motion or labyrinth disorders. The third major pathway is the chemoreceptor trigger zone.
This is a part of the brain at the base of the fourth ventricle. It's functionally outside of the blood brain barrier, so it's able to sample the bloodstream and the CSF. And it projects to the vomiting center through intracerebral projections with dopamine type two, 5-HT3 and neurokinin type one being the key receptors. And this mediates nausea due to drugs, metabolic products, bacterial toxins, basically anything that can be in the blood or the CSF. And then the fourth pathway is what we call the peripheral pathway, and this is really all of the parts of the body outside of the CNS that can contribute to nausea and vomiting.
Some of the key parts are the 5-HT3 receptors in the gut and mechanoreceptors and chemoreceptors in the GI tract, serosa and the viscera. These all project to the vomiting center through the vagus and splanchnic nerves, a sympathetic ganglia and the glossopharyngeal nerves. This mediates nausea due to mechanical stretch, such as in a bowel obstruction or stasis. GI mucosal injury, for example, by radiation or chemotherapy or local toxins or drugs. So if you understand these four pathways, you can determine which pathway and which receptors are involved in the patient's symptoms.
Then you can move on to step three, which is choosing an antiemetic to block those receptors. >> Yes, so that leads to the question of how you apply this mechanistic approach to direct clinicians to the appropriate therapy, and so how would you approach that? >> Maybe we can talk about this best with examples because I know it sounds really complicated when I go through these four pathways, especially for listeners that may not have a diagram in front of them. So maybe we can just go through a couple examples. First example I'd use is the aphagia patient and you do a complete history and physical, and you think, this patient's nausea must really be caused by that radiation that they just started that's involving their GI tract.
So that's what your cause is. That's step one. Step two is you try to think what pathway is involved. And that's probably the peripheral pathways, and you think it's probably that radiation is damaging the enterochromaffin cells in the patient's gut causing serotonin to leak out and bind the 5-HT3 receptors in the gut. And step three is you choose the antiemetic to block the implicator receptors, so you choose ondansetron which is a 5-HT3 antagonist. Another example is that you do a good history and physical when you have a patient you think having a lot of vertigo and has an nystagmus on exam, and you think that tumor we see on the imaging that's near the vestibulocochlear system is probably causing the patient's nausea and vomiting.
So step two is which pathway is involved, and that would be the vestibular system via acetylcholine and histamine type one receptors. Step three, you choose the antiemetic to block those receptors, so maybe you choose a scopolamine patch, which is an anticholinergic medication. >> You mentioned several pharmacologic therapies. Are there others, and are there also non-pharmacologic approaches that may be effective? >> Well, there are certainly other pharmacologic therapies, and we sort of talked about how to choose your antiemetic.
There are also some basic principles I want to highlight about how you prescribe the antiemetics. What you want to do after you go through those three steps and pick your right antiemetic is you want to schedule it around the clock for as long as whatever is causing the nausea is expected to persist. And then taper it to as needed dosing. If one antiemetic isn't enough, you generally add a second antiemetic that blocks a different receptor that may be involved in the patient's symptoms. And I'm glad you asked about non-pharmacologic approaches because these are often forgotten and can actually be very helpful.
So these are things like avoiding triggers for the nausea and vomiting, limiting oral intake when the symptoms get really bad, using relaxation techniques. There is some data that suggest that P6 stimulation, P6 is the region in the wrist that's stimulated either by acupressure or maybe even wristbands that that can help with nausea. And then surgeries or other inventions can sometimes be very helpful, things like stents or venting G-tubes, depending on the situation and the goals of care for the patient.
>> Is there anything else you'd like to tell our listeners about managing intractable nausea and vomiting in patients at the end of life? >> Well, sometimes even if you follow this mechanistic approach and have multiple antiemetics blocking different pathways scheduled around the clock, there may still be patients who have persistent symptoms. And for these patients we consider less traditional agents. We think about dexamethasone, olanzapine, mirtazapine, and cannabinoids, and there's some evidence for each of these that they may provide some benefit. We also consider alternative roots, such as rectal preparations or oral dissolvable tablets.
The key message, however, that I'd like to leave you with is that the best way to treat nausea and vomiting is to get at the underlying cause. And I think that's where this thoughtful, step-by-step mechanism-based approach is really powerful because it forces you to think about why the patient is having the symptoms. So you can not only choose the best antiemetic regimen, but so you can also address that underlying cause. So for example, if a patient is nauseous from thrush, the best antiemetic regimen in the world will not be as good as just treating that thrush.
So you do your careful evaluation. You figure out the cause. You figure out which pathway and which receptors are involved. You choose antiemetics to block those receptors, and then you always, always, always try to address the underlying cause if possible. >> Thank you, Dr. Wood, for your insights into managing intractable nausea and vomiting in patients at the end of life. For additional information about this topic, JAMAevidence subscribers can consult Chapter 7 at Care at the Close of Life.
This has been Joan Stephenson of Jama talking with Dr. Gordon J. Wood for JAMAevidence.
Segment:0 .
>> I'm Joan Stephenson, editor of JAMA's Medical News and Perspectives Section. Today, I have the pleasure of speaking with Dr. Gordon J. Wood about managing intractable nausea and vomiting in patients at the end of life, which is a topic in Care at the Close of Life discussed in a chapter co-written by today's guest expert. Dr. Wood, why don't you introduce yourself to our listeners? >> Thank you for having me. My name is Gordon Wood. I am the director of Palliative Medicine and Supportive Care at Northwestern Lake Forest Hospital in Lake Forest, Illinois.
I also attend on the in-patient palliative care consult service at Northwestern Memorial Hospital in downtown Chicago. Additionally, I'm an associate medical director at Midwest Palliative and Hospice Care Center in Glenview, Illinois. >> Dr. Wood, I know that nausea and vomiting are very common symptoms at the end of life. What is meant by intractable nausea and vomiting, and what type of patients are at risk for it? >> Well, the formal definition that we use for intractable nausea and vomiting is nausea and vomiting that's not adequately controlled after multiple anti-emetics are used in series and/or in combination.
Practically speaking, though, I use the same sort of mechanism-based approach for every patient near the end of life who is bothered by nausea and vomiting. What I mean by mechanism-based approach is sort of a three-step approach. First step is doing a thorough evaluation to determine the cause of the nausea. The second step is using knowledge of pathophysiology to determine the receptors involved. And finally, the third step is choosing anti-emetics which block those receptors. Unfortunately, I get to use this, you know, frequently because a lot of patients near the end of life develop nausea and vomiting.
Some of the more common scenarios are patients requiring opioids for pain control. A lot of patients tolerate these well, but some patients have very severe symptoms of nausea and vomiting. Sometimes patients receiving chemotherapy or radiation, especially if the radiation is to the GI tract, patients with brain tumors, and the really tough ones seem to be patients with altered anatomy. And that could be from a malignant bowel obstruction or from things we do to them, like gastroesophageal stents or other surgical or interventional alterations of the anatomy.
>> So what are the first steps that clinicians should take to evaluate nausea and vomiting in patients at the end of life? And also, can you describe some examples of clues that clinicians can look for to determine the cause? >> Well, what I really try to do is take a really systematic approach, and I do a head-to-toe approach, and I think it works really well. And what I mean by head-to-toe approach is I sort of start at the top and for each part of the body I try to think of the causes of nausea and vomiting that could come from that part of the body, and that helps direct my questions and my history and also what I do in my physical exam.
So just sort of going through this briefly, I start with the brain at the top, and the causes there are increased intracranial pressure or meningeal irritation, anxiety, and any of the five senses. So I ask about things like headache or whether the patient feels nausea come on while they're driving to their chemotherapy session. Next down in the head-to-toe approach is the ears. I think about the vestibular system and motion-induced nausea or labyrinth disorders, so I'm asking about vertigo. I'm looking for a nystagmus on my exam.
Next down is the nose, so I ask about post-nasal drip. And then next down is the mouth, so I look for thrush or herpes. And then next down is the esophagus, so I ask about symptoms of GERD. Next down is the abdomen, and there's lots of causes here; gastritis, peptic ulcer disease, stasis, bowel obstruction, gallbladder, liver, pancreatic disease, bowel compression by a large spleen, GI radiation. I try to ask about all of these types of symptoms and ask about it in my history and then examine for them on my exam.
For example, one of the things we try to do is get people to characterize their nausea. If they describe nausea that is a large volume and happens infrequently or the vomiting happens infrequent and when they throw up, it relieves the sense of nausea that can be a sign of a malignant bowel obstruction or a partial bowel obstruction. Next down on the head to toe is the rectum. That makes me think of constipation. I ask about that in detail, and I do a rectal exam. And then once you've gone sort of from the brain all the way down to the rectum, you think about systemic causes that are throughout the whole body, so these are medications like opioids, antidepressants, antibiotics, chemotherapy, endocrine causes like adrenal insufficiency, electrolytes and other metabolic issues like hyponatremia, hypercalcemia, renal failure, liver failure, bacterial toxins, and then ask about these.
So did they just start a new antidepressant and maybe that's why they're nauseous, or did they just stop a steroid and maybe their adrenally insufficient. So this sort of head-to-toe approach I think is the key way that I approach the evaluation of a patient with nausea and vomiting. >> Dr. Wood, you started at the head in your evaluation, and that leads to the question, what role does the brain play in intractable nausea and vomiting? And why is it important for clinicians to understand which neural pathways may be responsible for a patient's symptoms?
>> Well, the brain is key because that's where all of the signals from all of those head-to-toe causes get integrated. If there are enough signals, the brain triggers the nausea and vomiting reflex. So understanding the neural pathways allows you to determine which pathways are involved in a particular patient's nausea. And then you can choose an antiemetic to block the receptors in that pathway. So there are four main pathways that all come together in the vomiting center. And the vomiting center is located in the brain stem, and the key receptors in the vomiting center are acetylcholine, histamine type 1 and 5-HT2.
So the first of the four pathways is what we call the cortex. And the cortex has direct afferents into the vomiting center. And this mediates nausea due to sensory input, anxiety, meningeal irritation and increased intracranial pressure. The second main pathway is the vestibular system. And this mediates vomiting via the vestibulocochlear nerve using main receptors acetylcholine and histamine type one. And this is responsible for nausea due to motion or labyrinth disorders. The third major pathway is the chemoreceptor trigger zone.
This is a part of the brain at the base of the fourth ventricle. It's functionally outside of the blood brain barrier, so it's able to sample the bloodstream and the CSF. And it projects to the vomiting center through intracerebral projections with dopamine type two, 5-HT3 and neurokinin type one being the key receptors. And this mediates nausea due to drugs, metabolic products, bacterial toxins, basically anything that can be in the blood or the CSF. And then the fourth pathway is what we call the peripheral pathway, and this is really all of the parts of the body outside of the CNS that can contribute to nausea and vomiting.
Some of the key parts are the 5-HT3 receptors in the gut and mechanoreceptors and chemoreceptors in the GI tract, serosa and the viscera. These all project to the vomiting center through the vagus and splanchnic nerves, a sympathetic ganglia and the glossopharyngeal nerves. This mediates nausea due to mechanical stretch, such as in a bowel obstruction or stasis. GI mucosal injury, for example, by radiation or chemotherapy or local toxins or drugs. So if you understand these four pathways, you can determine which pathway and which receptors are involved in the patient's symptoms.
Then you can move on to step three, which is choosing an antiemetic to block those receptors. >> Yes, so that leads to the question of how you apply this mechanistic approach to direct clinicians to the appropriate therapy, and so how would you approach that? >> Maybe we can talk about this best with examples because I know it sounds really complicated when I go through these four pathways, especially for listeners that may not have a diagram in front of them. So maybe we can just go through a couple examples. First example I'd use is the aphagia patient and you do a complete history and physical, and you think, this patient's nausea must really be caused by that radiation that they just started that's involving their GI tract.
So that's what your cause is. That's step one. Step two is you try to think what pathway is involved. And that's probably the peripheral pathways, and you think it's probably that radiation is damaging the enterochromaffin cells in the patient's gut causing serotonin to leak out and bind the 5-HT3 receptors in the gut. And step three is you choose the antiemetic to block the implicator receptors, so you choose ondansetron which is a 5-HT3 antagonist. Another example is that you do a good history and physical when you have a patient you think having a lot of vertigo and has an nystagmus on exam, and you think that tumor we see on the imaging that's near the vestibulocochlear system is probably causing the patient's nausea and vomiting.
So step two is which pathway is involved, and that would be the vestibular system via acetylcholine and histamine type one receptors. Step three, you choose the antiemetic to block those receptors, so maybe you choose a scopolamine patch, which is an anticholinergic medication. >> You mentioned several pharmacologic therapies. Are there others, and are there also non-pharmacologic approaches that may be effective? >> Well, there are certainly other pharmacologic therapies, and we sort of talked about how to choose your antiemetic.
There are also some basic principles I want to highlight about how you prescribe the antiemetics. What you want to do after you go through those three steps and pick your right antiemetic is you want to schedule it around the clock for as long as whatever is causing the nausea is expected to persist. And then taper it to as needed dosing. If one antiemetic isn't enough, you generally add a second antiemetic that blocks a different receptor that may be involved in the patient's symptoms. And I'm glad you asked about non-pharmacologic approaches because these are often forgotten and can actually be very helpful.
So these are things like avoiding triggers for the nausea and vomiting, limiting oral intake when the symptoms get really bad, using relaxation techniques. There is some data that suggest that P6 stimulation, P6 is the region in the wrist that's stimulated either by acupressure or maybe even wristbands that that can help with nausea. And then surgeries or other inventions can sometimes be very helpful, things like stents or venting G-tubes, depending on the situation and the goals of care for the patient.
>> Is there anything else you'd like to tell our listeners about managing intractable nausea and vomiting in patients at the end of life? >> Well, sometimes even if you follow this mechanistic approach and have multiple antiemetics blocking different pathways scheduled around the clock, there may still be patients who have persistent symptoms. And for these patients we consider less traditional agents. We think about dexamethasone, olanzapine, mirtazapine, and cannabinoids, and there's some evidence for each of these that they may provide some benefit. We also consider alternative roots, such as rectal preparations or oral dissolvable tablets.
The key message, however, that I'd like to leave you with is that the best way to treat nausea and vomiting is to get at the underlying cause. And I think that's where this thoughtful, step-by-step mechanism-based approach is really powerful because it forces you to think about why the patient is having the symptoms. So you can not only choose the best antiemetic regimen, but so you can also address that underlying cause. So for example, if a patient is nauseous from thrush, the best antiemetic regimen in the world will not be as good as just treating that thrush.
So you do your careful evaluation. You figure out the cause. You figure out which pathway and which receptors are involved. You choose antiemetics to block those receptors, and then you always, always, always try to address the underlying cause if possible. >> Thank you, Dr. Wood, for your insights into managing intractable nausea and vomiting in patients at the end of life. For additional information about this topic, JAMAevidence subscribers can consult Chapter 7 at Care at the Close of Life.
This has been Joan Stephenson of Jama talking with Dr. Gordon J. Wood for JAMAevidence.
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