Friday, October 23, 2020

Chlorpromazine in Delirium FTW!

by Drew Rosielle (@drosielle)

David Hui, Eduardo Bruera, and colleagues have published another important delirium trial out of MD Anderson which I thought was worth blogging about in detail.

In some ways it's related to the same group's RCT a few years ago of lorazepam added to haloperidol for agitation in hospitalized advanced cancer patients with delirium (showing the lorazepam quite effectively reduced agitation via presumably a sedating effect). As I pointed out in the Palllimed post about that trial, while they labeled their patient group as 'agitated delirium in advanced cancer', in essence it was really a sedation for terminal delirium trial as most patients only lived a few days, but a casual reader of the study might not realize that and think they were finding that lorazepam is a disease-modifying therapy for delirium. Which it is not, discrete exception aside (alcohol withdrawal?).

This is an important distinction, as I think there's been a sort of confusion over the years in our discussions about delirium and even research about it between disease-modifying therapy for delirium and essentially palliative-focused therapies to reduce distressing aspects of delirium (primarily agitation). Eg, a drug or drug combo or other intervention that reverses delirium / shortens delirium / returns normal cognition vs a therapy that reduces agitation (because while you could reduce agitation by 'fixing' the delirium you could also do it by sedating the patient). When and whom to just sedate is often complicated, but frankly less so in our patients who have 'terminal delirium' or 'agitation,' insofar as this implies the patient is imminently dying, it is not expected we can reverse the underlying cause of the delirium, and (most often) the goal is to prevent and mitigate suffering during the patient's final days, which in reality ends up meaning sedating the patient (not in a deep, continuous, so-called 'palliative sedation' way, but enough to quiet the distressing motor restlessness etc).

This is a long-winded way of expressing my appreciation for the investigators who, for this study, describe their goal as reducing terminal agitation in advanced cancer patients with delirium, and not treating delirium per se, which is much appreciated.

The trial: this is a single-center, double-blind, parallel-group RCT trial of hospitalized cancer patients at the MD Anderson palliative unit. Basic inclusion criteria were patients had to have a RASS score of 1 or more during the prior 24 h despite being on their group's standard, first-line delirium/agitation therapy which is scheduled + rescue haloperidol (which per their protocol could have been anywhere from 1-8 mg a day, but it's a little confusing and they also note that all the enrollees were put on 2 mg haloperidol q6h scheduled + 2 mg q1h prn before going onto the study drugs protocol). Subjects were randomized in a 1:1:1 fashion to haloperidol dose escalation, switching haloperidol to chlorpromazine, or additing chlorpromazine to haloperidol.

Interestingly, they didn't however clearly define the 'terminal' part of their goal of studying terminal agitation. For what it's worth, this is a study within a single institution's palliative unit, and they basically say that any patient getting to their unit in such a state is very likely to be 'terminal' and they left it at that.

They had a complicated double-dummy design using pre-made syringes of study-drugs/placebo, but essentially patients received one of:

- 2 mg haloperidol q4h scheduled + q1h prn
- 25 mg chlorpromazine q4h scheduled + q1h prn
- 1 mg haloperidol + 12.5 mg chlorpromazine q4h scheduled +q1h prn

If this was inadequate (RASS 2 or higher), doses were essentially doubled in a stepwise fashion. This Table from the Supplement outlines the protocol, it's a bit complicated.

Their primary outcome was the change in RASS at 24 hours. The secondary outcome was the proportion of patients with a RASS score of -2 to 0 at 24 h (basically, that was their goal, to keep patients between -2 which is 'lightly sedated,' and 0 on the RASS).

They randomized about 45 patients between the arms, mean age 63 years, 83% white, and all had a KPS of 30% or less.

There was no difference between groups regarding RASS reduction at 24h, or proportion of patients with a goal RASS at 24h. Most subjects' RASS scores went down about 3 levels (eg from 1 to -2), without differences between treatment arm at 24h.

Nearly all of the other secondary outcomes were the same between groups.

But, a couple of the secondary outcomes that did show differences did seem to favor rotation to chlorpromazine: fewer patients in the rotation to chlorpromazine needed rescue medication in the first 4 or 8 h after blinded drug/s were administered (big differences here, eg 19% in chlorpromazine vs 73% in the haloperidol escalation group at 4 h), and fewer in that group also needed a dose escalation. Ie, although the study wasn't really trying to determine this, their data are suggestive that in the chlorpromazine arm (25 mg q4h scheduled), patients "more rapidly" achieved the desired RASS state than the other arms. They got more comfortable appearing (more sedate) faster, and stayed there, compared to the other arms. I believe these were post hoc analyses, not prespecified secondary findings, so take them with a grain of salt, however the differences were quite marked, and I'm basically persuaded here. Chlorpromazine FTW!

Median survival was 48-72 h in all groups. No differences in side effects/harms between groups were evident.

Bottom line here: escalating haloperidol, rotating to chlorpromazine, or doing a little of both are equally helpful in getting terminally agitated patients more comfortable appearing at 24 h, but switching to chlorpromazine is probably the fastest method.

So, pretty good study. To me, it's an argument that I should be rapidly switching to chlorpromazine when I think death is imminent (days) and a few doses of haloperidol have not achieved much. There's a confusion of options out there, more haldol, chlorpromazine, other sedating neuroleptics (eg quetiapine which I kinda hate but is used all the bleeding time it seems [not by my team], and while this study obviously didn't look into all the options I'm in favor of really making chlorpromazine the drug of choice (when sedation is acceptable, the goal).

For more Pallimed posts about delirium.
For more Pallimed posts by Dr. Rosielle click here.

Drew Rosielle, MD is a palliative care physician at the University of Minnesota Health in Minnesota. He founded Pallimed in 2005. You can occasionally find him on Twitter at @drosielle.

Friday, October 23, 2020 by Drew Rosielle MD ·

Monday, October 19, 2020

Patient Access to Notes is Coming! Is Palliative Care Ready?

by Christian Sinclair (@ctsinclair)

Patients and families across the US are about to get a close look under the hood of electronic health records in just a few weeks. Starting in November, the 21st Century CURES Act is putting in place the rules for patient access to their health records including the clinical notes of the clinicians. Your organization is possibly planning for this new access to be flicked on like a light switch in the inky dark of night. Some of you may be shocked and seeing this for the first time, some of you have seen glimmers, some of you are well prepared, and some have had your eyes long adjusted and are probably thinking, “What’s the big deal with patient access?”

Patient access to notes feels like it should be in our wheelhouse. It is about communication, patient-centeredness, and talking openly about hard truths. But understandably without much preparation, many palliative care and hospice clinicians are going to feel underprepared, which may cause a lot of anxiety. But there is hope! And time! Well, a little bit of time, but still time!*

If all of this is news to you, I would encourage you to first spend some time on the OpenNotes website - The group started over a decade ago to help clinicians and patients navigate this potentially tricky territory so that both can benefit. It is not directly related to the CURES act nor responsible for the implementation. The OpenNotes site has great resources, tips, videos and links to research of what other specialties have been exploring like adolescent patients and confidentiality, mental health, and caregivers.

Second, if you are on Twitter, definitely follow friend of the blog, Liz Salmi (@TheLizArmy), and OpenNotes on your preferred social media platform (Twitter, Facebook, LinkedIn, YouTube)

Third, newly armed with some information, go talk with your colleagues at your organization and your leadership about what local resources and info you need to know. Do your note templates need to change? What will you be telling your patients and families to expect? How will your group handle sensitive information that you would not feel comfortable immediately sharing with patients and families? How will this impact your collaboration with other teams when you have conversations via your notes?

Fourth, now that you have thought about it and notified the people you work with, make time to attend some online Q and A sessions organized by the OpenNotes team. This Wednesday, October 21th from 5-8pm ET, there will be a live AMA (Ask Me Anything) on Reddit (r/medicine) with myself and a number of other colleagues who will be taking questions on the ins and outs of OpenNotes. Next week on October 29th 11a-Noon ET, I will be giving a Grand Rounds Webinar with the group at OpenNotes. It is free to register, and I hope someone from your group will take time to attend.

Lastly, If you have any tips, tricks, questions, please add them in the comments below. I will work hard over the next few weeks to stay on top and get them answered!

Now, let’s review your plan:
1 - Read the OpenNotes website for practical information and research.
2 - Go follow key people on Twitter who talk about patient access to notes.
3 - Talk to your colleagues at work and your leadership to prepare for patient access to notes.
4 - Register for the webinar and check in on the Reddit AMA.
5 - Leave tips, tricks and questions in the comments below.

Christian Sinclair, MD, FAAHPM, is a palliative care physician at the Univeristy of Kansas Health System working in outpatient palliative care and leading the research group there. When he is not fixing the order of the 'i' and the 'a' in the word pallaitive, he can be found coming up with unneccessary acronyms.

*And speaking of time, I do want to apologize for not banging the drum on this earlier and louder. I have been a fan of the work OpenNotes has done for a long time, and sharing my notes for the past few years. The CURES act was passed into law in late 2016. The final rule and timelines were finalized in Spring of 2020. I should have been much louder about this, but with COVID, it did not seem as critical until it got much closer, and now it is nearly here. So I am working to make amends!

Monday, October 19, 2020 by Christian Sinclair ·

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