Advanced Pain Management in Cancer: Janet Abrahm

Eric: Welcome to the GeriPal Podcast! This is Eric Widera.

Alex: This is Alex Smith.

Eric: And Alex, who do we have with us today?

Alex: Oh, I’m so happy to welcome to our podcast Janet Abrahm, who is a dear friend, teacher of mine from back in the days of residency and fellowship. Taught me everything I know about symptom management for patients with cancer.

Janet Abrahm is a Professor of Medicine at Harvard Medical School and Dana-Farber Cancer Institute, and the Department of Psychosocial Oncology and Palliative Care. She’s the author of the fourth edition now of Comprehensive Guide to Supportive and Palliative Care for Patients with Cancer, along with co-authors Molly Collins and BR Daubman. Janet, welcome to the GeriPal Podcast.

Janet: Thank you. Delighted to be here.

Eric: On this podcast, we’re going to be focusing on the management of cancer pain. We’ll talk about some pharmacological, non-pharmacological ways to think about it. But before we get into the topic, Janet, do you have a song request for Alex?

Janet: I absolutely do. Alex, would you please play Truckin’ by the Grateful Dead for me?

Alex: And why this song?

Janet: Well, I was a Deadhead in college.

Eric: So was I.

Janet: This is one of my favorites. It went on forever.

Alex: That’s a good reason. We have recorded, I think, probably around 236 podcasts. And shockingly … I am shocked … But I believe you are the first person to request the Grateful Dead. I also love the Grateful Dead. My first concert was Grateful Dead in Ann Arbor back in, I don’t know, the late ’80s.

Janet: Yeah, Jerry was still alive. Yeah.

Alex: Gary was still alive.

Eric: Alex, Marin is a kind of a … Isn’t Phil Lesh … Doesn’t he have Terrapin Crossing? The Farm?

Alex: Yes. Yeah. A lot of the Grateful Dead members live around here, and they lived around here probably when they wrote this song, on the break from their travels around the country.

Janet: Absolutely.

Alex: Classic Grateful Dead tune. All right, here’s just a little bit.

(singing)

Janet: Beautiful. Thank you.

Eric: All right Janet, I got to ask the question: Fourth edition of this book, hundreds of pages in it. I always like to ask: what motivated you to even start writing this book? Let alone the fourth edition, but the first edition?

Janet: Well, the first edition came about because I had a lot of good stories about my patients, and what I’d learned from them. And my husband, who’s a poet, had a really interested editor who said, “You really need to put these stories down, because you have a lot to share with people.”

So back in 1999, really, the first edition came about. And then each edition is a testament to how much I’ve learned. Because I knew no psych stuff, being an oncologist back in 1999, who would’ve taught me what “affect” meant? Nobody. So then I went to Dana-Farber to learn from Susan Block and her colleagues.

And then every edition since, it reflects what my patients and my colleagues have taught me. This time, it really needed an overhaul because of the LGBTQ issues, because of interpreter issues, because of the fact that the words “minority” and “non-minority” don’t make sense anymore. There was just so much.

Also, I had really encouraged people to take opioids back in the early 2000s, because that’s what we were doing then. Nobody was taking them. We didn’t have pain as a fifth vital sign then. All of that really had to be revamped in terms of opioid safety.

So I was really excited to bring in a couple of co-editors who were young and hip, and at the cutting edge of palliative care now, along with my collaborators: the social workers, the psychiatrist, a chaplain to really make this book relevant for now. That’s the main thing.

I would say the drugs didn’t change as much as all the stuff about sexuality and about family dynamics and spirituality: all the things that I’m hoping people will get from this book.

Alex: It’s a wonderful book. The word in the title is absolutely correct: comprehensive guide. It has chapters on so many aspects of palliative care and supportive care for people with cancer. Today, we’re going to focus on management of pain and other distressing symptoms … probably. We’ll see if we get to other distressing symptoms.

We’ll start with pain. There may be some talk about hypnosis. I don’t know if one of us is going to be hypnotized on this podcast. We’ll see what happens, listeners, today.

I wanted to ask you about some medications that are sort of hot medications, that only palliative care experts seem to know a lot about. Well, maybe palliative care and a few other select specialties. Maybe we’ll start with ketamine. What is the role of ketamine in treatment of symptoms for patients with cancer?

Janet: Well, this is really controversial, because there have been so many conflicting studies about whether ketamine works or whether ketamine doesn’t work. I’ll have to share with you my clinical experience and my reading of the literature.

What we use ketamine for is the patient who has become often hyperalgesic on standard opioids like Dilaudid. We were asked to [inaudible 00:06:38]-

Alex: Wait, can we stop there one sec? I love getting refreshers for our audience who may not remember, because I always have to look it up.

Janet: Oh, okay.

Alex: What’s the difference between hyperalgesia and allodynia?

Janet: Allodynia kind of is before hyperalgesia. Allodynia means that you’ve changed the sensation. So your C fibers, instead of reflecting touch anymore … I mean your A fibers, instead of reflecting touch anymore, start to reflect pain, start to conduct pain. Whenever you’re touched, you have pain.

Alex: So allodynia is like pain in response to a sensation that is ordinarily not painful, like light touch.

Janet: Exactly right. Light touch.

Alex: And then hyperalgesia-

Janet: If you look the spinal cord, you can see that that’s what’s happening. That there’s activation.

Hyperalgesia is a central nervous system toxicity, neurotoxicity, such that there is spread along the spinal cord. So that a touch one place hurts another place. There’s myoclonus involved. There’s often maybe even delirium involved; it’s like when you have a very bad sunburn, and you go to touch that area of the skin; just a light touch will turn very painful.

When we see this is with well-meaning clinicians who are increasing … Usually it’s a Dilaudid drip in a cancer patient with really bad neuropathic pain, meaning the pain is from the nerve that was injured. So when a nerve’s injured, it keeps firing. And when it does that, spinal cord changes and there’s lots of little chemicals there that stop the opioid from working. So you have to go up and up and up on the dose. And when you do that, you go up and up and up on the side effects if you’re using a drug like Dilaudid.

So we get called to see somebody who’s every time you touch them anywhere, they’re in pain. The nurses say we can’t touch them anywhere.

Alex: That’s the allodynia.

Janet: Yep.

Alex: So they have both allodynia and hyperalgesia.

Janet: They often do. Exactly.

Alex: And myoclonus, potentially.

Janet: And they’ll have myoclonus unless they’ve been on a benzo for their anxiety. They don’t rule it out just because they don’t have myoclonus.

Alex: I would say that hyperalgesia, myoclonus hyperalgesia described also as wind-up. Is that right?

Janet: Yes.

Alex: Wind-up of the nervous system.

Janet: Yes. That’s what I meant about the spread. That sensation spreads up and down the spinal column so that one hurt, one touch, one place can hurt someplace completely different.

Alex: I think that’s probably one of the symptoms that I miss most: true confessions of a practicing palliative care physician. I worry that I miss that often. Particularly with patients in our hospice unit who are often not on IV fluids, getting dehydrated, getting ever-escalating doses of IV Dilaudid. And then I don’t know what to do about this pain. I suspect that part of that’s hyperalgesia.

Janet: It is. And you may have missed the turnoff between delirium and pain, or your nurses may have. So that when the patient is moaning, it’s actually because they’re delirious, and the opioid is making things worse. [inaudible 00:10:03]

Alex: We started off talking about ketamine. Should we get back to ketamine?

Eric: Well yeah, before ketamine, our options for treatment for hyperalgesia: A, you can lower the dose of the opioid; you can do an opioid rotation; or you can do ketamine. Are those the three potential options?

Janet: I would say that to do the opioid rotation, you often need the ketamine, so that the opioid rotation and ketamine go hand in hand.

Eric: Yeah. I’ve used ketamine a couple times in over 15 years of doing this. And our challenge is the only place we can do ketamine is in our ICU. Now we have to transfer that patient, so we often do opioid rotations without it.

But honestly, right now in our hospice unit, once I start getting into higher and higher doses, I recognize earlier on that just pouring more of the same in often is not the best approach. So I’m using adjuvants like methadone, or switching to other agents much sooner than I did 15 years ago.

Janet: I think that’s such an important insight: is that neuropathic pain does not respond to any opioid but methadone, really. In your hospice unit, if the Dilaudid isn’t working; and again, you’re not doing lots of CAT scans in your hospice unit and so forth.

But if you can imagine, usually often that the retroperitoneum, for example, is involved, at least in a cancer patient. There’s usually a cause, a neuropathic cause that’s subtle like retroperitoneal nodes or invasion of the plexus in the pelvis or the plexus in the lumbosacral area.

Eric: Rectal cancer patients-

Janet: Oh my gosh.

Eric: Ovarian it is so hard because of that plexus being…

Janet: So what we’ve taught our fellows; actually, what my fellows taught me; is, why are we making these people toxic? Why don’t we just start on methadone? And I thought “Duh, yes.” Joel Carter taught that to me, Alex.

So if I know a person has rectal cancer or ovarian cancer or uterine cancer or a colon cancer that’s recurrent in those nodes, I start with methadone. There’s no reason not to.

Eric: And you’re doing methadone to start off with? 2.5 or five?

Janet: Yeah, BID. Usually these people will have been on something that I can transition, because I get them referred to me. So they’ll have been on something that I then immediately transition to methadone.

Eric: I loved in your book, because I think the number one thing is people don’t realize methadone is both a short-acting agent and a long-acting agent. And initially, it’s just a short acting agent. It takes a while to build up its long-acting activity. Can you describe that for me?

Janet: Sure. I just want to be clear that the person in the book isn’t real. One of my fellows thought the person was real. I just want to say I made that person up. She said, “But it’s so real.” I want a disclaimer there.

Yes, methadone is short-acting and long-acting. In somebody, especially who’s been on something like Dilaudid, what I’ll do when that Dilaudid pushes are not working, which they’re usually not, I’ll substitute a methadone PRN.

I usually give methadone three times a day because it’s such a good reliever; it’s so exquisitely sensitive neuropathic pain. If they feel great by day two, I know I’ve overdone the methadone and I have-

Eric: Methadone PRN.

Janet: Yeah. Again, you have to be careful. We watch them carefully. But somebody who is not responding to the Dilaudid PRNs; and I’m sure you’ve seen those people. You’re giving four or six of Dilaudid PRN and nothing happens, IV.

Alex: IV.

Janet: That’s person’s going to get myoclonic and neurotoxic weight because they’re not responding. So in that person, I would give five of methadone. You can give a Q6. I usually tend to give a Q12 PRN. But you can give a Q6 PRN.

Eric: We started using methadone PRN, somebody who’s on around-the-clock methadone, and then also using methadone PRN with pretty good results.

Janet: Oh, good.

Eric: I’ve never really done that, because I’ve always worried about the half life of methadone is heterogeneous, and exceptionally long in some folks. So the idea of using that as a PRN scares the bejesus out of me.

Janet: Well, are these people at home or in your unit?

Eric: Both.

Janet: Well, at home I would really want a good observer in the home that was really reliable, who would tell me if the patient … not the first day. I mean, if they’re in really bad pain and they go to sleep, they’re supposed to go to sleep because they finally have their pain relieved.

Alex: That’s awesome.

Janet: But if they’re sedated the next day, then that might be a sign not to use the methadone PRN anymore, or to lower the standing dose.

Alex: Getting back to ketamine, for those who have access, who are able to use ketamine in settings like the wards or in their hospice units or their palliative care units: I wish it were so for us, so we didn’t have to transfer patients to ICU. How would you use ketamine to treat hyperalgesia?

Janet: What the ketamine really does is allow you to lower the opioid drastically, because that’s what you want to do. You want to go back to where they were before they got hyperalgesic.

Like the patient we saw who’s on four an hour of Dilaudid. Then we come back in the next day, and they’re on 12 an hour of Dilaudid because the team missed the turnoff. There, we want to go back to four an hour. It’s hard to explain that to the family. They’re in terrible pain, and we’re going to lower the dose. But that-

Eric: And I always thought with ketamine too, thinking about how to actually do this, I always thought you got to decrease the dose of the opioid when you start ketamine. Do you keep the opioid? Let’s say they’re on a Dilaudid infusion; do you keep that the same, or do you decrease it by half?

Janet: No. That’s what I’m saying; is that I only use ketamine because people don’t like being dissociated from themselves, mostly. Because that’s a side effect: they don’t like saying, “Oh, who is that?” I use it when they’re toxic, so I need to lower the dose of the opioid.

Also remember, it’s a pure NMDA agonist. So it’s really going to be a good pain reliever in that patient, because the problem here is that you need to block that NMDA activity so the opioid will work. The advantage of methadone is it blocks the NMDA, and it binds the opioid receptor.

But in the three days it takes, or five days it takes for the methadone levels to rise, you need to give them something that will deal with the pain, and that allows you to lower the Dilaudid dose, if you will, while you’re giving. I usually leave the Dilaudid, I add the methadone, but I lower the Dilaudid back to where they weren’t toxic and I add the ketamine. So I do all three things at once.

Alex: This is IV ketamine?

Janet: This is IV. Again, I look it up every time. I mean, I looked it up for this talk. There’s nothing magic about it. There’s a recipe in the book.

Eric: There is, page 308. I’m looking at it right now. You got a beautiful…

Janet: Little practice box. Because who remembers?

Eric: The little practice box tells you exactly what to do.

Janet: I think it would be dangerous to remember it, to be honest. This is one of the things you want to look up every time you use it. And you want to go over it, the DAG with your colleagues, with the nurses, with the nurse manager; you want everybody to feel comfortable, and let them know what the side effects are. And also look happy about-

Alex: That disassociated feeling?

Janet: Yeah. And let them know that that’s how their patient’s going to feel. Let the family know. Also, alert them that if they do get hallucinations, you want to use a benzo.

Alex: Benzo.

Eric: Why benzo and not an antipsychotic?

Janet: I don’t know why, but that’s what works. The antipsychotics don’t work in hallucinations induced by NMDA inhibitors. I’m not-

Alex: I think that was on my palliative care boards.

Janet: Oh, my gosh.

Eric: Technically Alex, I don’t think you wrote that. You say you’ve agreed to the boards, you’re not going to say what you…

Alex: Oh, okay. Right. That may have not been on my palliative care boards.

Eric: All right, I got a question for you.

Alex: Wait a minute. You got that one wrong.

Eric: Any other practice pros on ketamine?

Janet: Those are the major ones. Oh, carefully pick your patient. You don’t want people who would be totally freaked out by dissociation.

Eric: Okay.

Janet: Because that’s not a good idea.

Eric: Oh yeah, I got a question.

Janet: I think it really works well. And I think it’s good to try to get that DAG, get your pharmacy colleagues to get it through. Talk to the nurses about it. Tell them that it’s really not dangerous. And you should be able to give it in your hospice unit, like we can in our intensive palliative care unit. We can’t feel like-

Eric: I feel like every two to three years our field falls in love with a new medicine.

Janet: Oh.

Eric: This year, buprenorphine. Buprenorphine is so hot right now in palliative care.

Alex: So hot.

Eric: So hot. Ketamine was hot topic for a couple years at HPM meetings.

Janet: It has its uses.

Eric: Yeah, about 10 years, maybe eight years ago it was all lidocaine. Lidocaine, lidocaine, lidocaine. Is lidocaine helpful?

Janet: I can’t say. In the patients I take care of, not really. Perhaps in chronic pain patients who don’t have cancer. I know that the anesthesia pain people give lidocaine infusions. I have not found it to be helpful, but the literature suggests that it is helpful. So I would not spend a lot of time on it.

Alex: Okay. How about-

Eric: So you really don’t use a lot of lidocaine anymore.

Janet: No, I never did, actually. I used other stuff, but-

Alex: Well, going back to buprenorphine, which is incredibly hot: what is the role of buprenorphine for cancer pain?

Janet: It’s tricky, because-

Alex: Give the advantages and disadvantages.

Janet: Yeah, advantages are, it’s a patch, put it on for seven days. It doesn’t induce as much respiratory depression, it’s good for neuropathic pain. I mean, it has a lot of good uses.

Eric: I want your opinion on this too, as we talk about pros and cons. Because a lot more people are getting immunotherapy. And there’s a concern for opioids with some immunosuppressant effect of morphine and other agents. And I’ve heard maybe buprenorphine may not have that same … I think this is all little hand wavy, hand wavy.

How do you feel about opioids, immunosuppression, and whether or not buprenorphine’s a better drug?

Janet: I don’t really know the data on fentanyl, buprenorphine, or methadone. The morphine family, there’s some pretty good data. But these are other families. Mellar Davis would know. He knows everything about this kind of thing.

Eric: Yeah.

Janet: If I was wondering about it, I would call Mel and say, “Is it okay for me to use in an immunotherapy patient?”

But the problem with buprenorphine in our patients is the limit on the size of the patch you can use in the US. Because of the QT prolongation, the biggest patch you can use is 20.

Alex: 20.

Janet: And that’s 80 of oral morphine equivalents.

Alex: Which often isn’t enough.

Janet: Way not enough. Now maybe a regular cancer patient population, not the palliative care population, it would be fine.

Alex: You were saying because of QTC issues?

Janet: Yeah, that’s why the FDA limited it. So that’s a problem.

Then there’s also the antagonist effect. For example, if you’re using it with other opioids, if you need to use high doses of other opioids: I’ve seen in somebody who was on Suboxone for example, but had more pain; she was on 24 a day of the Suboxone, the buprenorphine equivalent.

But as we started the methadone, she really got into a withdrawal situation. So we had to stop the buprenorphine and just give methadone. Then we got her up to the level she needed for pain, and for suppression of craving. But that can be very tricky. And it has the same problems of fentanyl with fevers.

Alex: Oh, yes, let’s talk about that. Fentanyl: there are those things that are probably not as well known as they should be. And that we go around teaching house staff every year, because it’s something they haven’t heard of.

And I think one of the things that you taught me … There’s so many things that you taught me that I find myself teaching, I’m like, “Oh, I’m channeling Janet again on the wards.”

One of them is that in patients who have cancer and who are on fentanyl patch, they often get febrile, right? They get neutropenic fever, so common. And that there’s issue with fentanyl and transdermal fentanyl and febrile patients. Could you talk about that a little bit?

Janet: Sure. The fentanyl patch is basically a delivery device to create a subq reservoir of fentanyl in the fat of a person. A, you have to have fat. And B, you have to show the nurse where to put the patch. Because the underarm area is the best place.

They end up putting it on the scapula. I’ve seen it on the clavicle, I’ve seen it anywhere that there isn’t any fat. And guess what? It’s not working, because there’s no subq reservoir.

So when you have a subq reservoir of fentanyl, if you get a fever, you get dilation of the arteries that go to that reservoir, and you get more absorption. And because cancer patients tend to be malnourished in general, they also have less albumin. So the refraction of the drug is going to increase if they get it all acidotic or septic. You have the double whammy of increased absorption and increased refraction, especially in malnourished people, that can really tip you over into respiratory depression.

Eric: Way back, I did a deep dive. Because sometimes, I like to nerd out on this. Because I kept on hearing about the fat thing.

Clearly, some studies looking at this increase absorption by 10 to 30%. And heat packs, hot tubs, hot showers, fevers, all can do it. My understanding is the cutaneous depot of fentanyl is actually in the very high layers of the skin, the stratum corneum, which is not fatty.

Janet: Oh.

Eric: You got this depot in the high layer, so absorption is really governed by the microcirculation to that stratum corneum and skin…

Alex: We’re going deep here – Eric said “stratum corneum. [laughter]

Eric: That’s probably why we see in cachectic patients, we see it’s a very huge variable absorption.

Janet: Doesn’t work. It usually doesn’t work. They usually have what I call a fentanyl vest, and they’re not decreasing the amount of PRNs allotted they use at all.

Alex: Yeah. Fentanyl vests; they’re just covered in fentanyl patches.

Eric: Yeah. I stop when it gets above 405. I’m like, “What? It’s not working anymore.”

Janet: Yeah, that’s right. And I think that there are a couple other caveats. I mean, it does take 12 to 18 hours. And they did very good studies on that. It’s a very acute rise of the fentanyl levels. So it’s going somewhere as a depot, for sure.

Now remember, also out these days the biggest barrier is the tattoo sleeve, because you can’t put it over the tattoos. And so many people nowadays, maybe it’s an East Coast thing. They’ll have a whole armful of tattoos, a sleeve.

Eric: Does the tattoo ink?

Janet: Through the ink, and there’s scar tissue there.

Eric: Oh …

Janet: It also won’t go through lymphedema, because there’s water there. I saw somebody withdraw one time.

Eric: Oh, wow.

Janet: Because it won’t go through water. So it’s tricky to use. But in the right patient, I think it could make all the difference.

Eric: Janet, I never pull up a fentanyl table. I just use the 2 to 1 rule, which is-

Janet: Me, too.

Eric: Yeah?

Janet: Yep.

Eric: You use 2 to 1?

Alex: Mm-hmm.

Eric: Can I have you describe what the 2 to 1 rule is?

Janet: Oh, that twice the oral morphine equivalent is twice as much as what the fentanyl patch is. If you have 100 OMEs, the fentanyl patch is 50.

Eric: Then you do a little dose reduction. And when you do that dose reduction, you come up with the same thing as the patch.

Janet: Well, I don’t do a dose reduction for fentanyl. I just-

Eric: Oh, you don’t.

Janet: No.

Eric: Why not?

Janet: Because of the way that numbers were derived. I’m listening to my pharmacist who was trained by Mary McPherson, so I know she’s right.

Eric: Amazing Mary McPherson says.

Janet: She says it. Bridget Scullion, who’s our head of our pharmacy program says it. I do whatever they tell me.

Eric: I got a question. Alex, is it okay if I switch back to methadone for a second?

Alex: Yeah, yeah. Go.

Eric: Okay, I got to ask because I’ve been talking with my fellows about this. What do you use for methadone conversion? Or do you use anything at all? Because you always come up with either five TID or 10 TID as your final outcome.

Janet: That’s right. Me too.

Eric: And you ever do anything other than 10 TID, you’ve probably done your math wrong. Do you use the methadone conversion?

Janet: I use the new one that everybody agreed on, which is also in the book. Just to mention that the proceeds of the book all go to my department; they didn’t go to me. Just want to make it clear.

Under 100, you start with a certain amount. And then there’s no ratio. Then from 100 to 200 OMEs, you divide by 10. And over 200, you divide by 20. Which is why it is an acetonic curve. Sometimes it comes out to five BID, though. Sometimes it comes out to five BID.

Eric: You never get out above 10 TID.

Janet: Actually, you can if it’s one of these patients. The question is, and I asked Westport this ages ago: “Do you ever start at more than 10 TID?” Because I’ve had patients on 10 an hour of Dilaudid. Right?

Alex: Mm-hmm.

Janet: That’s 240 of Dilaudid a day. So that’s 240 of methadone a day. IV Dilaudid. I’ve had a patient on 10 an hour of IV Dilaudid, getting a little myoclonic. That’s 240 of IV Dilaudid, multiply it by 20 for the OMEs, divide it by 20 for the ratio. And you’re at 240. So what do you do with that? I don’t know.

What I do with that is 10 TID, to be honest. But that’s the kind of patient I would use methadone as the PRN. That’s the kind of patient I would use that on.

Eric: And what would you use your PRN dose? Five? 10?

Janet: I would start with five.

Eric: Five.

Janet: There’s no data on this. I’ve just noticed that it’s safe. Remember, I only do inpatient care, so I can watch these people really carefully. I haven’t gotten into trouble with it, to be honest.

Alex: Right, right, right.

Janet: I’ve got in more trouble with the people getting myoclonic and hyperalgesic from the Dilaudid. And that’s with all the adjuvants. Of course we use adjuvants.

Alex: Right, right.

Eric: Okay, I got another. Alex, can I switch subjects?

Alex: Please.

Eric: All right.

Cancer neuropathic pain from their chemotherapy that they had.

Not on any opioid yet. Not on any treatment. What’s your go-to first line?

Janet: So you’re talking about the neuropathy, the peripheral neuropathy?

Eric: Peripheral neuropathy.

Janet: You’re not talking about neuropathic pain. Yeah, you’re talking about peripheral neuropathy

Eric: Peripheral neuropathy, hands and feet.

Janet: The data is really awful on this. The data does show that gabapentinoids don’t work for this. And they only-

Eric: But everybody’s on a gabapentin drug.

Janet: Yeah, but they shouldn’t be. It’s just toxicity. It really doesn’t work for that. I mean-

Eric: Well, I think it’s the sedation that probably helps, right.

Janet: … if they have another reason.

Alex: They’re so sedated, they don’t care.

Janet: I mean, if the patient has another reason to have neuropathic pain, like shingles, like cancer invading their nerves. Go for the pregabalin, no question. But duloxetine is the only drug that has been shown to be helpful in platinum-induced and taxane-induced peripheral neuropathy.

The most important thing on that is prevention these days, guys. So if you’re asked, cold hands and feet, big difference. To prevent peripheral neuropathy is using cold packs on the hands and feet. Very good studies showing that that makes a huge difference in preventing peripheral neuropathy. Once it’s there, it’s really a problem to treat.

Eric: So drugs that you think may cause peripheral neuropathy? Cold packs.

Janet: Well, while they’re getting it. There’s a specialty-

Alex: While they’re getting the drug.

Janet: … afoot.

Eric: Oh, so keep it away from those nerves.

Janet: Yes.

Eric: Decrease the circulation for your hands and your-

Janet: Yes. And there’s no data that that increases relapse or anything like that.

But it’s really powerful. And people who are getting these repeat, repeat, repeat doses of FOLFOX and things like that, that get it so often; having cold in the hands and feet has made all the difference from Taxol.

The other drugs have not shown to be helpful in chemo-induced peripheral neuropathy because you’ve killed those nerves, basically. Don’t people tell you they feel like they’re walking around in pizza boxes? I mean, the nerves are dead. If they’re burning, then you might as well try the pregabalin if they’re burning.

Eric: And why pregabalin over gabapentin?

Janet: Because it’s linearly absorbed.

Eric: So better bioavailability.

Janet: Much, much better bioavailability. Gabapentin, after about 600 a day, or in a dose after more than 400 in a dose. Remember, there’s an active transport metabolism for gabapentin, if we’re nerding out here. When you get higher doses, it’s just not transported across the gut. Period. You’re getting 25% of what you’re giving this patient at enormous cost.

Usually, if the patient doesn’t respond to 300 three times a day, insurance will let you give the pregabalin, because they’re generics now.

Eric: Can I ask? When you do that, let’s say somebody is on 900 milligrams gabapentin a day. You’re all, “This ain’t working. I want to try pregabalin.” Do you just stop the gabapentin and start the pregabalin?

Janet: No, you just switch.

Eric: Or do you titrate the gabapentin down?

Janet: You can just switch. You can just switch.

Eric: Because it’s the same mechanism of action, right?

Janet: Yeah. It’s the pre-drug, really. Gava is the pre-drug of gaba. It’s the same mechanism of [inaudible]; you just substitute depending on what their dose is. So 300, you could start anywhere from 50 to 100. I mean, depends on what the side effects are that you’re worried about: sedation and so forth. Somebody’s on 900 three times a day, I give them 100, 150 three times a day.

Eric: Of the pregabalin, 100, 150.

Janet: Yeah. Because you get a cleaner drug. If we could get insurance approval all the time, I would only use pregabalin, because you know it’s being linearly absorbed.

Eric: It should become generic soon, shouldn’t it?

Janet: I think so. So we can look for that.

Alex: So the most difficult cancer-related pain … I mean, there’s a lot that are challenging to treat. But the one that’s most common, that I find very difficult to treat, is radiation-induced mucositis in the mouth and the throat and the esophagus. Any thoughts about treatment for radiation-induced mucositis?

Janet: Again, we’re treating patients with radiation-induced mucositis. I actually find that somewhat hopeful, because it’s going to go away.

Alex: Yeah, right. It’s so limited.

Janet: Well, I have a couple of strategies. Of course, a PCA; that’s well known to be the right treatment, because you push the button when you’re swallowing; besides all the topical treatments. But because it’s a neuropathic pain, methadone is good for that too.

Alex: Ah, I have not tried that.

Janet: And you could put the liquid methadone in the feeding tube, can’t you?

Alex: Ah.

Janet: Also, the pills dissolve completely. If you can’t get the liquid for some reason, methadone tablets dissolve completely in water.

Eric: So you can use the tablets in the feeding tube, too.

Janet: Well you wouldn’t use the tablets. No, you would dissolve the tablet in water first.

Eric: And then-

Janet: Then put it in the feeding tube if you can’t get the liquid.

But to have a low level of that, especially in somebody who’s at week three of head-neck radiation, you know things are only going to get worse for the next five weeks, and they have a low threshold and are just out of their minds. Because there’s always some chronic pain. It isn’t always when they swallow. So methadone is my secret go-to, and it works really well.

Alex: That’s great. We have to get to hypnosis. What is the role of hypnosis? And how did you become interested in hypnosis as a treatment for symptoms and cancer?

Janet: Remember, I started back with the Grateful Dead, right?

Alex: Mm-hmm.

Janet: So I started caring for cancer patients a long time before we had good agents that were long acting. Also, I believe in the power of the mind to concentrate and affect sensation, very much so.

My grandmother had a family physician who used hypnosis with her. So when I started doing oncology, and all I had was morphine and Percodan and Compazine, This is before Zofran, this is before MS Contin. I had methadone also. That’s why I’m so comfortable with methadone; that was my long act. I thought, “There must be something else I can do.”

So there’s a wonderful organization called the American Society of Clinical Hypnosis that gives trainings from Thursday afternoons to Sunday mornings, different places every month in the country. I thought, “I bet I could do this. I could use imagery and I could help people be someplace they’d really rather be, which is good. Or I can help them connect to their bodies in spooky ways.”

So I got trained. Then when I worked with my sickle cell patients, they’re like, “Yeah, we do that all the time. How do you think we deal with the crisis pain? Because nobody’s giving us pain medicine.” Remember the day when nobody would give a sickle cell patient pain medicine?

Alex: Yeah.

Janet: Or I would work with a patient with nausea and vomiting to help her be somewhere she’d really rather be. So that she vomited, but there was no affect associated with the vomiting. She would just vomit, and then she could get through her treatment.

Also, you could just change things with kids. You can do eye surgery, because they can be looking at a TV and you don’t have to anesthetize them and you can do strabismus surgery.

Alex: Wow.

Janet: It’s a very powerful technique. And for people who have stopped being able to swallow because of their mucositis getting better, I talk about a river and the water running through. You bring in all the senses. I used to do it for bone marrows all the time. I would take them out to wherever they wanted: the woods or the ocean, and bring in all the senses and the sounds.

One guy said, “I know what you’re doing. I want to go to the mountains, not the ocean.”

“Okay, we’ll go to the mountains.”

My fellow was so funny. She said, “For the next three months I smelled cider donuts every time,” because we did cider donuts.

It connects you so beautifully to your patients. You can make tapes. It used to be tapes, but you can do a phone recording for them. You can really help them, as I said, in a place where they’d really rather be and decrease the anxiety component. And you can change pain colors.

Eric: Janet, can I ask? A lot of what I’m hearing, it sounds like there’s some relaxation techniques.

Janet: Yes.

Eric: Potentially breathing. We know distraction is incredibly important when it comes to pain. But I think probably a lot of people, they have their own stereotypes of what hypnosis is. You have that person with the watch, he-

Janet: I never use a watch.

Eric: … hypnotizes you and you start-

Janet: Acting like a chicken.

Alex: Acting like a chicken. [laughter]

Eric: Right.

Janet: You have to do an education beforehand. You have to say, “You’re not going to do anything that you wouldn’t otherwise do.” I’m convinced of that, because I’ve done a lot of training in hypnosis. “You’re not going to do anything you wouldn’t otherwise do. What we’re going to do is just enhance your ability.”

I’ll say, “When you’re at a really good movie, you don’t notice that four people have moved in next to you and are crunching on their popcorn. You don’t hear that. You’re watching the movie.” And when you wake up it’s like, “Wait a minute, this theater was empty when I came here.”

You give them an introduction that it’s the same focus. “We’re just going to help you not hear things you don’t need to hear, and focus your imagery on …” It’s different than just distraction, because…

…like I would burn my hand on a frying pan, then I’d put it over here because I could get the image of cold there. And my husband would say, “Oh, you burned your hand again.” And I wouldn’t blister.

Or I had somebody in the lab who cut his hand on some glass, went to the ED. He was a Russian. I said, “Remember what the feeling is of cool snow, fresh snow in your hand? Let’s get that feeling of that cool, fresh snow.” I used an alcohol swab to induce it. He stopped bleeding.

Your autonomic nervous system responds really well. There’s lots of wonderful things that you can do, and it can feel so powerful. It certainly doesn’t take the place of things. But for many of my patients, it’s a wonderful adjunct, waiting for the pain medicine to kick in, or just getting more power back. It’s really marvelous.

Alex: Also, one of the things that really appeals to me about this is that connection that you form with your patient: doing this hypnosis, guided imagery.

And you’re on the journey together.

Janet: Yes. Then you bring them back with as much as they want to bring back, as much as they’re comfortable bringing back. That’s what you say when you’re trained.

People do therapy with this. I don’t do dentistry with it. I don’t do OB with it. I don’t do psychotherapy with it. I just do medicine with it, or palliative medicine with it.

And I do it without induction, because patients are already induced. You know that look: when they’re not swallowing, they’re listening to every word you’re saying: that’s a patient already induced. All you have to do is be really careful with your words.

Don’t say, “This is going to hurt a lot.” Say, “You may feel something. I don’t know what you’re going to feel. I wonder what you’re going to feel.” That’s why I’m so intent about words. That’s the other thing it’s taught me is I cannot bear to hear somebody say, “You failed the chemotherapy, you failed the treatment.” Because that patient hears, “fail.” The treatment isn’t working anymore. But that’s why they ask you, what should you eat differently or what should I do?

I can’t bear to hear the ICU team say, “We’re going to withdraw care.” Because that literally is what that family hears next door. “Oh gee, I wonder when they’re going to stop caring for my loved one.” So hypnosis has taught me the power of words, for good and for harm.

And there will be coming an enhancement with me doing a hypnotic induction online later in this year. There are a lot of enhancements connected to the book where we’ll show you the things we talk about, like communication topics and hypnosis and what to say at the end of life to families.

The book is just one aspect, and then we’re hoping to improve your skillset by showing you how to do these things. I promise to do it when my voice is better, though.

Eric: Do you think more palliative care teams should have somebody trained in hypnosis?

Janet: I think that would be really helpful. And I wish there were more. Yes. I think that it’s an underused, really powerful specialty. And it’s easy to get trained.

Eric: Yeah. Well Janet, I really want to thank you. There is so much more in your book. Really want to encourage all of our listeners to check it out.

Janet: Thank you.

Eric: We’ll have links to where to buy it on our Show Notes. But before we end, I think Alex is gearing up for a little more Grateful Dead.

Janet: Oh, wonderful.

Alex: (singing)

Eric: Well, Janet, very big thank you for joining us.

Janet: You’re welcome.

Eric: … and for writing this book.

Janet: You bet.

Eric: Really loved reading it.

Janet: So glad. Thanks for everything.

Eric: And as always, thank you Archstone Foundation. And to all of our listeners, thank you very much for supporting the GeriPal Podcast.