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by Drew Rosielle

(This is the third of four posts by Drew on the language we use in hospice and palliative care. You may want to read his reflection on 10 years of practice or his other posts on euphemisms - "Comfort Care," and "Compassionate Extubation." - Ed.)

"Palliative Sedation."  Golly I hate this one.

Frankly 'terminal sedation' was better, because it was at least less confusing, but  neither of them are clear or transparent, and particularly 'palliative sedation' is just so confusing and potentially laden with too many meanings to be ever useful. There are so many clinical scenarios out there in which someone is sedated (deliberately, or as an aftereffect of trying to control pain/anxiety/dyspnea/etc; deeply or lightly; continuously until death vs temporarily as respite) in circumstances that the average person would agree would be 'palliative' or 'of-palliative-intent' that the term is useless.

There have been some people in the literature who call it some variation of 'deep, continuous sedation,' which I like a lot better, because it's a basically accurate description of the practice, at least the practice which is meant most of the time by 'palliative sedation' but not all the time, which sometimes gets contrasted with the 'proportionate palliative sedation' moniker, because there are so many different types of sedation-which-is-palliative, and OH MY GOD, right?

If we have a term which needs so much parsing, we need a different term.

If the thing you are talking about is deliberately inducing a state of unconsciousness, and keeping a patient in that state until they die, as a means of controlling otherwise uncontrollable symptoms in a dying patient, 'deliberate, deep, continuous sedation in a dying patient' seems about as accurate and parsimonious as you could get. There are people who propose this sort of sedation as a temporary measure, which I've never done, but you could then say 'deliberate, deep, respite sedation for severe symptoms' or some variation. If what you actually mean is aggressively managing symptoms with drugs even if some level of sedation is the consequence, then just say that, and not the reactionary, befuddled 'proportionate palliative sedation' monstrostiy.

Besides the ridiculously confusing nature of the phrase 'palliative sedation,' it's another example of the myriad ways in which 'palliative' is used: care-which-is-palliative, care-which-is-given-by-a-palliative-care-team, palliative pediatric cardiac surgeries, palliative chemo, used synonymously with 'comfort care', 'going palliative' etc etc. It just makes it worse for us to have the term pegged to this practice which, strictly defined, seems to happen very rarely in the US (deliberate, deep, continuous sedation), and reinforces an image of our care teams as people who just drug the hell out of patients. I once met a hospitalist who shook my hand and said to me kind of as an aside 'You know, I'm very pro-palliative sedation," as if he expected me to make eye contact and nod, in some sort of manly acknowledgement that I understood how forward thinking and progressive you are, what a friend to palliative care you'll be.

In all honesty, I thought to myself "OMG you are an idiot and I don't like you and I bet you're not comfortable with your patients' existential pain." Turns out, first impressions really are accurate, but that's another story. 

Drew Rosielle, MD is a palliative care physician at University of Minnesota Health in Minnesota. He founded Pallimed in 2005. For more Pallimed posts by Drew click here. 

Illustration Credit: Christian Sinclair CC-BY-SA-NC

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by Kevin Madden, MD

Just as in any medical specialty, there are “bread and butter” aspects of Pediatric Palliative Care – situations we encounter on a frequent basis that we are quite comfortable in dealing with.  Pain management, constipation, family meetings, resuscitation status and discussions about goals of care certainly are at the top of that list.

What: #hpm (hospice and palliative med/care) chat on Twitter
When: Wed 3/2/2016 - 9p ET/ 6p PT
Host: Kevin Madden MD Follow him on Twitter @madden_kevin


If you are new to Tweetchats, you do not need a Twitter account to follow along. Try using the search function on Twitter. If you do have a Twitter account, we recommend using tchat.io for ease of following. You can also check out the new site dedicated to #hpm chat - www.hpmchat.org

Photo credit: ZebraPen.com

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The 4 Questions:

"During your child's end-of-life care period, did you or a family member ever consider asking someone on the care team to give him/her or give you or the family member medications to intentionally end his/her life?”

"When your child was receiving end-of-life care, did you or a family member ever discuss intentionally ending his/her life?"

"Did you or a family member ask someone on your child's care team to give him/her medications or to give you or the family member medications to intentionally end his/her life?"

"Did a member of your child's care team give your child medications or did you or a family member give him/her medications to intentionally end his/her life?"

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

19 (13%, about 1 in every 8) said they had thought about asking a doctor to hasten their child's death

13 (9%, almost 1 in every 10) actually discussed it with caregivers

5 (4%) explicitly asked a clinician for medications to end the child’s life

3 (2%) reported that their child’s life was intentionally ended with medication. In all three cases the medication used was morphine.

36% (49 of 136, about 1 in every 3) in retrospect, would have considered discussing HD under certain circumstances with a breakdown of scenarios given.

Uncontrollable pain was the most common circumstance to elicit a hypothetical consideration of HD. 15% would have considered HD for non-physical suffering.

Only 2 parents would have considered HD in circumstances not directly related to the child’s experience, (family witnessing suffering or medical costs).

94% endorsed proportionately intensive symptom management for a terminally ill child with uncontrolled excruciating pain, while only 54% did so in the case of coma; these results did not change when adjusting for race and religiousness.

50% (1 in every 2) endorsed HD in at least one vignette. 59% would agree with a physician discussing HD in the case of a child with terminal cancer in pain or coma.

Of the 19 who considered HD during their child’s EOL course 16 (84%) endorsed HD in vignettes.

In general, being white (not Hispanic) and being not very religious were associated with endorsing HD in vignettes.

Dussel V, Joffe S, Hilden JM, Watterson-Schaeffer J, Weeks JC, & Wolfe J (2010). Considerations about hastening death among parents of children who die of cancer. Archives of pediatrics & adolescent medicine, 164 (3), 231-7 PMID: 20194255

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This Sunday's New York Times had a front page/below the fold article on 'palliative sedation' (which as of last night was still the #1 most emailed article according to their website). It is a long, confusing article, & I'm still trying to figure out what I think of it. Like most newspaper articles about things like this it gets some things it gets spot on, while others I found deeply troubling.

The article tells the stories of several dying patients and their families, as well as interviews with palliative care physicians and other clinicians. The overarching theme of the article seems to be that 'PS' is controversial and ethically suspect - many doctors wouldn't talk about it directly with the journalist, 'slow euthanasia' charges are brought up, etc. The article also seems to recapitulate the generalized confusion out there as to what palliative sedation/terminal sedation is - and while it starts out as seeming to be about the practice of 'continuous/deep sedation' it confusingly then gives at least one patient story which is not about CDS (it's instead about a dying patient who became somnolent in her final days who also was receiving sedating comfort meds but did not receive CDS).

What it does well, and serves as a prime example of, is the anguish and distress that alterations in consciousness in dying patients cause our patients and their families. The loss of communication and personhood that accompanies the loss of consciousness, and the reality that many patients and families frequently attribute it to comfort meds and not the dying process, is repeatedly illustrated in the article. To be clear, absolutely the meds we use to treat symptoms in the dying (opioids, benzodiazepines, etc.) contribute to alterations in consciousness and I don't mean to suggest otherwise: what the article illustrates however is the pervasive unease families have about this, and the failure of clinicians to adequately allay these concerns. Not to make families 'happy' about the devil's bargain of 'more alert/more suffering' vs. 'less alert/less suffering' that occurs frequently in the imminently dying - it sucks and there's no getting around that - but the sense from the article is that many of these family members have persistent and unaddressed emotional and informational troubles about this, and that's a problem.

Aspects which troubled me:

• There is no mention of the (yes incredibly preliminary and by no means rigorous) investigations into PS practices which do not suggest it frequently hastens death (see for instance here: I by no means think this is any sort of definitive evidence, but it's an indication that people are beginning to try to answer these questions and thus far are not coming up with much to suggest current sedating practices hasten death).
• The article associates PS with rationing care at the end of life (ie clinicians being urged to hasten things along with PS to save money etc.). It does this by essentially saying 'boy PS could be used this way' then notes that no one thinks it is - but this is a sort of journalistic guilt by association (bringing it up then shooting it down) even if there is no one anywhere who thinks this is a significant problem.
• Every time it mentions sodium thiopental it notes it is also used as part of a lethal injection cocktail. Nice. So is potassium chloride, one of the most widely prescribed and used meds out there, but who's counting.
  
• One of the photos is of a patient who is described as resisting a DNR order for sometime, who at some point prior to her death agrees to it. They have a photo of her signing her DNR order - in the photo her doctor is actually holding the patient's hand with the pen in it (as if to steady it, etc.) - but given the overall tone of the article the (usually slumbering) paranoid part of me wondered if that image was deliberately chosen to suggest the patient was pressured into signing it against her better judgment, etc.
• There is no presentation of any patients for whom sedation (whether CDS or not) is seen as a good, welcomed thing (by either the patient or family). For every patient discussed in the article their sedation was presented as emotionally fraught, troubling to either the patient, or the family, or even the clinicians. As I mention above, this is absolutely fair, but in my experience it's just as common for family members to greet the mention of deliberate sedation with relief and gratitude: 'thank you for not letting my love one die suffering like they have been,' etc. I scanned some of the comments online and many of them spoke positively about sedation (either 'I'm glad the doctors did it so my loved one didn't die in pain' or 'When I'm dying I hope someone is willing to make me comfortable even if it means this') - it's too bad the article didn't present this perspective.
  

It's also possible that my reaction to the article is one of weary defensiveness and not wanting to see our community's 'dirty laundry' aired, particularly in a way that I think confuses more than clarifies, and makes it dirtier than I genuinely believe it is. I've rambled at length about this before on the blog - read the end of this post if you're interested.

As I mentioned before, I have very mixed feelings about the article, and would appreciate others' comments and thoughts.

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We don't typically endorse products, webinars, conferences, job listings or much of anything else here at Pallimed, but when we do know about a resource that can impact your everyday palliative care work we want you to know about it.

Such is the case with the Hospice and Palliative Care Formulary USA ($75/$65 for AAHPM members) now being published in the 2nd edition from the founders of PalliativeDrugs.com, Robert Twycross and Andrew Wilcox.  I wanted to write in more detail about why I access this book more often than any other palliative care book since I just ordered 6 of them for the teams I work with.

The first edition was printed in 2006 and my copy is dog-eared from carrying it around, showing it to hospice team members, lending out to fellows, residents, nurse case managers, copying a page for a pharmacist, referencing it for numerous presentations, etc.

Any other medication reference book (nursing or medical) has so many warnings/misinformation about the medications we commonly prescribe and administer in palliative care settings that general pharmaceutical reference books are essentially useless.  I often find nurses and physician trainees who read some of those freebie/cheap Nursing/Medical Drug Guides begin to contradict basic palliative care understanding.

For some poor examples from referencing other drug guides...

"We can't give more than 5mg of morphine...the book says she might have respiratory depression."
"Octreotide? I don't see anything about small bowel obstruction but it does treat a VIPoma."
"Constipation? How about we try more fiber?"

Here is why I find HPCF-USA so useful:

• Detailed palliative care oriented medication information
• Extremely well referenced drug monographs - Awesome for talks
  
• FDA Approved indications clearly listed as well as likely palliative care uses
• Cost information (in actual dollars not some crappy $-$$$$ scale)
• Candid discussion about alternate route dosing/administration for many medications
• Detailed pharmacologic information in tables to compare different meds within a class
• A treatment monograph on 'Oxygen'  - When was the last time you read 4 detailed pages about the ins and outs of oxygen therapy? Wonderful!
• Monographs on related but not primary palliative care meds - A whole section on antifibrinolytic drugs! Bronchodilators! Diabetes meds! Potassium! Magnesium!  You get the point.
  
• Super helpful chapters covering meds in a meta-approach - Opioids and Fitness to Drive; Continuous Subcutaneous Infusions; Drugs Administered via Enteral Tubes
• Designed for use in the USA (as opposed to the UK version with UK only meds like diamorphine)

Here are the things I wish were included/changed/fixed:

• Better binding - it seems to be fragile after a lot of use, and my book gets used
• Not much info on fentanyl IV compared to transdermal and buccal routes
• The 2nd edition cover is a little boring compared to the Red, White and Poppy motif on the 1st edition.
  

If you are an AAHPM member you can get a 20% discount via the AAHPM website.  Also you could access it online via PalliativeDrugs.com but I find the book very useful and a rapid access to have at my desk.  And now with the extra copies I purchased it will be at almost all of my clinical sites.

Do you use HPCF-USA?  Tell me what you like best about it.

Disclaimer: No kickbacks given to any Pallimed author because of this post.  We did give away a HPCF-USA free edition back in 2007 for our winter contest.  And it was pretty cool when I met Robert Twycross in Austin and he recognized my name from Pallimed and told me he was a big fan of Pallimed.  But that is not why I wrote this.  Obviously I think this is a super awesome book.

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Annals has a review of 'last resort' palliative sedation techniques (this makes two Tim Quill papers in a month in Annals). It begins with an apparently true story of a home hospice patient who was denied 'total sedation' despite refractory symptoms and requesting it (patient had to fire the hospice, and a previous palliative care consultant physician managed deep sedation for him over the phone: crazy).

The paper attempts 3 things: first, it tries to clarify the language used to describe sedating practices at life's end; second, it discusses ethical controversies about sedation; and third, it makes some practical suggestions that palliative sedation should be practiced by organizations only with explicit policies, procedures, and quality control.

The language proposed in the paper are three phrases:

1. Ordinary sedation: attempts to relieve a symptom (e.g. anxiety) without trying to alter a patient's level of consciousness. (I don't know why this then would be called 'sedation' as opposed to, e.g., anxiolysis with a medication which can have a sedating side effect, but that's not really important here.)
2. Proportionate Palliative Sedation (from the article): sedating medications (usually benzodiazepines) are progressively increased alongside other symptom-relieving measures, resulting in increasing levels of sedation during both waking and sleeping hours to help relieve suffering. It is usually initiated in response to otherwise intractable physical suffering in imminently dying patients, as in the case described, for example, or for agitated terminal delirium. The end point is relief of suffering that is acceptable to the patient by using the minimum amount of sedation needed to achieve this goal.
3. Palliative Sedation to Unconsciousness: This is what has variously been known as 'terminal sedation,' 'continuous deep sedation,' etc. Deliberately, pharmacologically, inducing a state of unconsciousness in order to relieve otherwise refractory symptoms, and with a plan of maintaining such a state until the patient dies (usually while withholding life-sustaining treatments otherwise such as artificial hydration/nutrition). They mention that this has been proposed, controversially, for existential suffering.

Fair enough; one might note that PPS and PSU in certain instances may, on the ground, appear identical (ie you rapidly sedate someone to unconsciousness for refractory symptoms), although a clinician's intentions might be different (PPS you are trying to control a symptom and 'happen' to need to use deeply sedating doses of a drug to do so; in PSU you've decided there's no way you can control symptoms otherwise, so you intentionally and from the start attempt to induce a pharmacologic coma).

One can appreciate that, in real life, what starts as PPS 'turns into' PSU in those rare occurances when you realize relief of suffering cannot be obtained without induction of unconsciousness, and that clinicians on the ground often don't spend too much time worrying about whether they are doing PPS or PSU. I also wonder that, with these definitions, and by describing PSU as a last resort practice, which it should be and I think by and large is used this way, one should argue that PSU should only be peformed after a trial of PPS, because how else can we be sure it is a last resort option? Which is another indication that trying to distinguish between these practices on the grounds of initial therapeutic goal (adequate sedation vs. coma) can't entirely account for real clinical practice - I think it's fuzzier. That said, there are times in which PSU is attempted from the get-go; for me it's when I conclude suffering is tremendous and death is very imminent (and I don't have hours or a couple days to tinker - or if I did it would be at the expense of ensuring a peaceful death) and you just go straight for deep sedation. Of course, I'd argue this is absolutely 'proportionate' when the alternative is a scenario when an imminently dying patient spends half their remaining hours suffering just so I can be 100% sure that I'm being 'proportionate.'

Which highlights the element of all this which I think they undersell in this paper: the question of imminence. It's actually barely mentioned, at least in frank terms. While they discuss ethical objections to PSU (as potentially death hastening, such as when artificial nutrition and hydration are withheld), such objections, to me, only have merit (which is not to say one has to agree with them) if one concludes that providing PSU is materially death-hastening (by weeks, months let's say). A declining, advanced cancer patient, bedbound, not taking much PO, who is developing altered mental status - this is someone who has days to maybe a couple weeks to live (generally speaking) - PSU without artificial nutritional support is unlikely to be death hastening, and if so by hours or a day or two. And if one is worried about hours or a day or two in dying cancer patients then we should all be debating about whether we should intubate and ventilate these patients to get them those precious days.

These questions have not been rigorously researched (there have been some preliminary attempts), and certainly would be difficult to study (e.g. prognoses of patients who have PSU performed, etc.). Along these lines the authors note that it's very difficult to tell in the palliative sedation literature what exact practice is being studied, due to the lack of agreed upon definitions of these practices. It's possible the authors don't believe imminence, per se, matters - it's less important than the refractory nature of the symptoms and lack of other options. Fair enough, but not foregrounding the importance of prognosis gives fuel to the fire that PSU is PAS-lite, or otherwise ethically suspicious. We all think in terms of risk-benefits; and the risk of a loss of two days vs 2 months, to me, are different.

Leaving my agenda aside here, the paper also gives important recommendations to all hospice and palliative care groups to establish sedation policies, procedures, checks, and quality control to both ensure the best possible care but to also mitigate potential for abuse or misinterpretation of these practices. I think one could also add we, as a community, should agree upon research definitions of these terms, to improve our ability to actually study sedation practices.

(Image is from an August Annals issue.)

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Annals of Oncology has a paper trying to look at whether palliative sedation is associated with shorter survival. It's a prospective, multi-center, single-country (Italy) study which prospectively matched ~270 cases (cancer patients admitted to hospice units who received palliative sedation) with similar 'controls' (similar cancer patients admitted to the same hospice units during the same period). Controls were matched for gender, age class (less than 65 and greater than 65 years), reason for admission (psychosocial, uncontrolled symptoms, and terminal phase), and Karnofsky performance status (KPS) subdivided into three classes (10–20, 30–40, and 50 or more). Patients who received PS did so based on standard practice by their treating physicians; there was also no standardization of PS treatments.

As you'd expect by the design patients were well matched; even though not deliberately matched the two groups ended up having similar Palliative Prognostic Scores, and so should have had grossly similar survival.

They admit that there are a variety of practices which fall under the umbrella of 'PS' and as far as I can tell they included anyone in PS group who received anything which the treating physician labeled as 'PS.' Along those lines, only 25% are described as receiving 'continuous, deep' sedation (ie what historically was described as 'terminal sedation'). There is a confusing array of data presented (some patients receiving mild sedation, others intermittent, some continuous but not deep, a whole variety of meds involved including opioids, etc.).

About 80% of patients received PS for delirium/agitation, with the rest being dyspnea and pain (and 6% for psychological distress only). The survival curves of both groups were identical (median survival in the 10 day range). They did not present separate data for just the 'continuous/deep' sedation group (and their controls). Cessation of artificial nutrition or hydration was not measured.

Their conclusion (from the abstract): "PST does not shorten life when used to relieve refractory symptoms and does not need the doctrine of double effect to justify its use from an ethical point of view."

Some thoughts here.

1. While I may think their conclusion is correct, that's not because this study particularly supports it. Most of the debate about PS has been about 'continuous/deep' sedation/'terminal sedation': essentially deliberately inducing a pharmacologic coma (state of unresponsiveness), with the intention of maintaining that coma until death (usually, although not necessarily, accompanied by cessation of other life-sustaining medical treatments including artificial nutrition and hydration). Only a quarter of these patients, apparently, had this flavor of PS, and we aren't presented with a separate analysis of these patients. Without doing that this is like arguing that light, intermittent sedation doesn't hasten death but that's not really a burning clinical or ethical debate currently.

2. This is a group of patients with a median survival of ~10 days. Even though this is a relatively large study, unless any intervention had a major impact on mortality demonstrating a difference in survival is nearly impossible. If they had given all the PS patients 1gm of pentobarbitol and a bucket of succinylcholine and found that median survival in the 'active' group was 5 minutes vs. 10 days for the controls that'd be one thing but this is not. The real point here is imminently dying patients are imminently dying patients and we're never, ever going to show a mortality difference between PS and non-PS groups of those patients. This sort of study design would be the way to do it - a randomized controlled study trial could not happen for ethical reasons. You could fancy this study up with a more elaborate propensity score matching process, etc. but it'd be essentially be the same study design. It's not going to show any difference however.

3. Is there a real, significant ethical question to be answered about continuous/deep sedation given for intractable symptoms in otherwise imminently dying patients? And is it in fact an important question to even be asking/worrying about - the potential for shortened life? Assuming CDS-PS is used as a last resort (ie nothing else has worked adequately, leaving aside questions about what that might actually mean) it seems the available therapeutic scenarios we have are:

1. Staying the course: patient dies with uncontrolled suffering in ~10 days.
2. CDS-PS without any life-prolonging medical care: patient dies peacefully in 10 days and yes, perhaps it's possible they would have lived 11 days without CDS-PS, or hell maybe we could have made them even live longer like a 12 days or 3 weeks if we mechanically ventilated them, put them on pressors, threw in some CVVH, and even tried a little ECMO.
3. Actively hastening death: applying novel medical interventions with the intention of ending life/shortening life; patient dies in less than 10 days with, well, no more suffering subsequently.
   

My point in throwing about ECMO in #2 there is to point out that in imminently dying patients questions of life-prolongation are really very secondary/unimportant (ideally speaking). If CDS-PS was shown to, let's say, halve survival from 10 days to 5 days, I would hope that no one would care. If they did, I'd ask them why not then string patients along a few more days on the vent then if what is most important is scraping a few more days of organ perfusion out of a dying patient's life?

I should not be naive: there are of course plenty of people for whom the thought of potentially 'hastened death' (really it's 'not-prolonged death') via deliberating sedating patients or using meds with sedating side effects is troubling. Research like this can be reassuring which is a good thing. I'm arguing however is that what is 'really' needed is not reassurance that these practices probably don't influence survival but engaging with clinicians who have these concerns about the fundamental issue: that it's ok not to prolong dying, that a peaceful, comfortable death should be the preeminent treatment goal when someone is dying and we don't need to twist ourselves into ethical knots about it.

4. The real ethical question about CDS-PS is whether it is an appropriate option for patients who aren't imminently dying (and I'm not going to define exactly what I mean by that), including for patients who have intractable psychological and existential suffering. In these cases, CDS-PS is almost certainly life-shortening and the question is is that acceptable? How much 'life-shortening?' How much suffering? This is a question that can't be answered by research.

Hat tip to Lyle for his thoughtful comments about this post.

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1)
BMJ has published a randomized controlled trial of a video-based decision support tool for advance care planning in dementia (related to this trial we blogged on a couple years ago; see also here). The video used is available in the free-full-text version on the BMJ website. This study invovled older patients who were randomized to a narrative description of advanced dementia vs. a video depicting a patient with AD, and asking subjects what sort of care they'd want. This is similar to the prior study but this study uses a separate control group (the prior one compared subjects' responses before and after seeing the video). As in the prior study, after seeing the video, the vast majority of subjects reported they'd prefer comfort-only measures and no life-prolonging treatments (86%, vs 64% in the written group). The video group's knowledge of dementia was better afterwards, and their treatment preferences were more durable (didn't change over time) compared with the written group.

This research is quite compelling: very simple and elegant in its design and execution, with compelling results. I am curious as to how it will be received in the general community (I guess I mean in primary care clinics where presumably this ACP should be happening) and if it will change anything, or if there are plans to bring this sort of ACP to the masses (e.g. public education campaigns, etc.). I don't do a lot of ACP for dementia (I get consulted on patients after they have dementia and family members are struggling with decisions) but do do a lot of 'ACP' about, for instance, CPR and it looks like Angelo Volandes (the doc primarily behind most of this research) is working on that very thing: http://www.acpdecisions.com/acpdecisions/Videos.html. I'm very much looking forward to the videos and what the research shows about their impact.

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The same BMJ issue has another part in the series I mentioned before on prognostic research: this one is on validating prognostic models, which is a relevant topic for Pallimed readers as we frequently discuss research on prognostic models and wonder how one can really judge their clinical relevance.

There's also a fascinating speculative article for pharmacology wonks out there and the generally curious about how psychiatric drugs work. I do not know if what the authors propose is 'correct' however it's always good to have one's paradigm's challenged. The core of their argument is as such:

An alternative, drug centred model of drug action, stresses that psychiatric drugs are, first and foremost, psychoactive drugs. They induce complex, varied, often unpredictable physical and mental states that patients typically experience as global, rather than distinct therapeutic effects and side effects. Drugs may be useful because some altered states can suppress the manifestations of certain mental disorders. The disease centred model of drug action developed in the 1950s and 1960s and replaced a drug centred understanding of how psychiatric drugs worked. For example, the early investigators of neuroleptic or antipsychotic drugs suggested that they worked by inducing a neurological syndrome consisting of physical restriction and mental symptoms such as cognitive slowing, apathy, and emotional flattening, which resembled Parkinson’s disease. These effects also reduced the intensity of psychotic symptoms. Thus, extrapyramidal effects, and their conjoined mental effects, were not regarded as side effects but as the mechanism by which the drugs produced their intended outcome.

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Lancet Oncology has a wonkish discussion of 'palliative sedation.' It's a somewhat searching, philosophical (literally: discusses personhood in the context of Descartes, Locke, Kant, and others), and meandering walk through the ethical controversies surrounding PS (they call it 'deep and continuous palliative sedation' when referring to the practice of deliberately pharmacologically inducing a coma with the intention of maintaining a patient in it until death in order to relieve intractable suffering). A lot of it focuses on the question of if inducing a coma extinguishes thought, does it therefore extinguish self-hood/person-hood, and if there's no intention of lightening the coma, is not one then 'killing' a person, and so is PS just a form of (or philosophically/morally equivalent to) euthanasia? Yes, I said it's wonkish, and while I don't think these Big Ideas are meaningless (and frankly enjoy thinking about them), and probably become more relevant the further PS gets away from a strategy to treat intractable somatic symptoms in otherwise dying patients, I also struggle with where the 'fancy' ideas get us.

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1)
Lancet has a fantastic article about pediatric palliative care. It's both a general overview of the field as well as a lively discussion of the Big Issues in pediatric palliative care (pretty much all of which will be familiar to practitioners of adult palliative care). It has case discussions involving concurrent palliative & curative therapy, palliative care for terminal illnesses which go on for years, cultural issues, suffering, hope, international issues, etc. You can tell I really liked it. Also, some sanity about 'denial,' probably one of the most over-used labels we (medical people, not necessarily palliative care people) apply to our sick patients:

Adults aware of their impending death might maintain hope by shifting from a hope for cure to hope for what they define as a good death (eg, as pain free and comfortable as possible) and with a focus on leaving a legacy. How to support hope for children with life-threatening illness is less clear. An additional challenge is the struggle for parents and other loved ones to maintain hope. What remains unexamined is the role of “healthy denial” in maintaining hope for cure despite a very poor prognosis. It is possible that for some children and parents “unrealistic hope” in the face of overwhelming disease is a functional coping mechanism that does not necessarily signify pathological denial. At times, people might hold beliefs that although seemingly discordant with each other (eg, the knowledge that one is about to die at the same time as maintaining hope for a last-minute reprieve from death) could instead represent healthy coping.

The same issue also has a review of cirrhosis with some good general info on general prognosis (although nothing much beyond this Fast Fact), prognosis after transplantation, and up-&-coming therapies (?maybe) aimed at directly slowing/reversing liver fibrosis. Interesting stuff, but nothing about supportive care.

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Archives of Internal Medicine has a couple.

First is an attempt of sorts to validate an anticholinergic risk scale. The ARS was developed to try to quantify how likely a certain drug is to cause anticholinergic side effects (falls, dizziness, confusion, dry mouth, constipation, dry eyes, etc.). The scale gives a drug a 0-3 (none to severe) score for likelihood of causing anticholinergic side effects and then a patient is given a risk score which is the sum of their individual drugs risk sub-scores (2+3+3 = 8 - this would be for a patient on one moderate risk and 2 severe risk anticholinergic drugs). This study attempts to validate the ARS (which was developed relatively empirically based on pharmacologic know-how) in a geriatric population (geriatric clinic patients) by looking at risk scores with actual symptoms and comparing geriatric patients with general primary care clinic patients (on the assumption that older patients are more likely to suffer anticholinergic toxicities). Essentially they found that the AR scale & score were decently predictive of toxicities, particularly in the elderly, and they conclude that the ARS is a reasonable way of identifying high-risk patients. (There is a table with the risk scale as part of the article).

The other paper is about 'delicate' issues surrounding 'continuous deep sedation' (also variably known as terminal or palliative sedation) in the Netherlands. It is based on a survey (36% response rate) of Dutch physicians, and much of the context of the study involves the fact that these physicians have euthanasia as an option for them as well as terminal sedation. I'll only comment on a couple findings. First is that these physicians overwhelmingly differentiated between TS and euthanasia, apparently largely due to intentionality - their intention with providing deep sedation was to alleviate symptoms as opposed to bringing about death in euthanasia. The other point is that the use of TS exclusively for non-physical symptoms (i.e. existential suffering) was relatively rare (~8% overall - rates are much higher than this for euthanasia). My overall gloss on this (and this is not the first bit of research out of the Netherlands to suggest this) is that - even in a setting where both practices are available - TS and euthanasia are conceived of differently by practitioners, and used differently for different situations/patients.

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Coincidentally, BMJ has a paper (again a survey) describing the epidemiology of the use of CDS in the Netherlands: how often, what reasons, use of artificial fluids/food, etc. Most physicians (again, this is all based on physician retrospective reporting) felt that it either didn't shorten life or did so on the order of less than a week. The one interesting bit here, and perhaps one that contradicts my earlier pontificating, is that rates of euthanasia are declining in the Netherlands whereas the percentage of people who die while receiving CDS is increasing which makes one wonder if one is being substituted for another...?

The accompanying editorial's subtitle is also worth mentioning: "Imprecise taxonomy makes interpreting trends difficult" and discusses the ongoing struggle involving language (TS vs PS vs CDS, etc.).

4)
Mayo Clinic Proceedings has two reviews. One is a discussion of informed consent - quite legalistic but a good basic review of the topic, its history, etc. The last section discusses autonomy and how patients actually want decisions made and I enjoyed this line: "Responsibility for medical care has landed on the shoulders of patients with a resounding thud."

The second is a review of small cell lung cancer. Picking up our on & off again habit of noting whether supportive care is mentioned in review articles of nasty, nearly uniformly terminal illnesses I'll point out that, in fact, there was no mention of anything like that.

5)
JCO has a really compelling reflective piece on death & blame. It starts off about patients/families blaming someone (oncologists, etc.) for the fact that treatment often doesn't work and then goes into a discussion about the place of death in our culture - is death fundamentally a wrong (in a deep moral and spiritual sense) or not? The problem is of course one can deeply believe that death is not wrong but that doesn't mean that 1) your patients agree, and 2) it doesn't deeply suck (hurts on the inside & the outside so to speak) anyway (to quote Christian quoting me - see the last post).

6)
Age & Aging has a study about a prognostic index for determining 4-year mortality for the elderly. It's based on prospectively gathered data on ~1000 patients from a single region in Italy and uses relatively easily obtainable data (could be obtained from a single office visit). Patients in the highest risk group had a 78% 4-year mortality - although it needs to be noted that only a very few patients fit into this group and so it becomes very difficult to interpret its validity. Indices like this are helpful in two ways: 1) as a research tool (risk stratifying subjects, etc.), and 2) to identify patients with more urgent indications for advance care planning, etc. What's unclear is if they offer anything further (clinically) than reinforcing the maxim that 'sick people are sick.' Thanks to Dr. Bob Arnold for alerting us to this.

7)
Finally, and don't call me crazy for noting this, JAMA has a primer about interpreting large genomic studies. It's likely that at least my generation will be faced with actually clinically useful genomic studies (about predicting efficacy/toxicities of opioids and other meds at the very least) and knowing what to make of these studies will be an important skill.

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1)
2 from Journal of Medical Ethics:

• First is one on terminal sedation and the 'imminence condition'. It's a difficult-to-summarize paper whose main point seems to be that the 'imminence condition' (continuous sedation to unconsciousness without fluids/artificial nutrition is OK as long as the patient is imminently dying and so withholding sustenance is unlikely to hasten death by much), which is endorsed by some proponents of TS, has not been fully explored in the literature and is full of holes (ethical analytical holes, you know the type). Never one to avoid whacking my clinician's head over an ethical analysis, the major issue I had with this is that the author repeatedly states that the imminence condition is not supported/explained by ideas of autonomy, proportionality, or double effect. However he never explains how proportionality fails to support the 'imminence condition.' I mention this because when I lead discussions on this I make the argument that it does (all of this is my opinion of course):
• Imminently dying (likely prognosis less than ~~few weeks) & intractable symptoms; potentially hastening death by providing deep sedation without artificial nutrition/hydration is proportionate to the alleviation of intractable suffering and the loss of several days of life. Vs.
  
• Not-imminently dying (prognosis of months) and intractable symptoms (existential or otherwise) --> here I think one can make a good argument for lack of proportionality between shortening life by months and alleviating the suffering. (Lord knows not all would agree with this, or with my first point above; my point however is that the concept of proportionality informs this discussion.)

• Second is a study on physicians' confidence in discussing DNR orders. In case you have any any doubts about its results, it indeed did find that we are far less confident in discussing 'code status' than other medical procedures, and that housestaff are less comfortable than attendings.
  

2)
Journal of Pain recently had a supplement on all things post-herpetic neuralgia. It has articles on the diagnosis, natural history, prevention (vaccination), etc. of PHN. The supplement is industry funded. A couple things to note:

1. The treatment article lists (in its summative drug treatment table) levorphanol as one of the opioid treatments (and not hydromorphone, fentanyl, or oxymorphone). This seems to be an idiosyncratic choice by the authors (i.e. not because levorphanol has been particularly studied for PHN). When was the last time you saw levorphanol mentioned in an article like this (except in an article suggesting it should make a comeback)? Anyway it's a good review article and mentions numbers-needed-to-treat as much as possible (although frustratingly fails to define what the NNT was for: e.g. 50% pain reduction?). One for the teaching file.
2. The mechanisms of pain and itch in PHN article is very readable, and morbidly fascinating (read the itch part). It has a lot of history and in some ways traces the history of thinking about chronic pain via examining the evolving understanding of PHN.
   

3)
Journal of General Internal Medicine has a series of articles on discontinuing implantable cardioverters/defibrillators (all full-free text). One on the ethics of doing so; one on patient attitudes about it (an incredibly depressing but thankfully small qualitative study in which none of the patients had discussed ICD deactivation or knew it was an option and seemed freaked out by even discussing it); and one on clinician attitudes about discussing ICD deactivation. Quote of the year:

"That’s like an act of suicide. It’s a threat to your life. That’s like cardiac arrest. That’s insane."

4)
A provocative little letter in CMAJ (free full-text here) about decision-making in impaired adults:

"Our colleagues in pediatrics, who face an equally limited decision-making capacity among their patients, have taken a more nuanced approach based on the following principles: children have dignity, intrinsic value and a right to medical treatment that serves their best interests; children should be involved in decisions that affect them; information should be presented truthfully and with sensitivity; decision-making should be interdisciplinary and collaborative; and the best interests of individual children should be of primary concern. We at CMAJ are surprised that such principles are not considered for adults with diminished decision-making capacity."

Their argument is that decision making capacity is not an all-or-nothing thing, and we should stop treating it as such. My feeling is that in real-life the above-mentioned principles are often considered for impaired adults, even if not explicitly stated (at times my group discusses the need for assent from our impaired adult patients even if we cannot obtain 'informed consent'). It's nice however to see these ideas in print.

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On the EBM front....

NEJM recently published a piece looking at publication bias in antidepressant trials (it looked at all trials of antidepressants which were registered with the FDA and compared those which were published in the literature and those that weren't). They found that the unpublished trials were much more likely to be negative ones, and that even several trials which the FDA deemed negative (not supporting the efficacy of antidepressants) were published with positive sounding results. This is not to say they aren't effective but that the magnitude of benefit may be over-estimated, and also sounds a (general) cautionary alarm when interpreting systemic reviews or meta-analyses which rely only on published research (particularly in areas in which there is a lot of industry-sponsored research and thus perhaps a lot of research which is never published).

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(Editor's note: Tom posted this on Saturday but it never got distributed by Feedblitz, our email updater, so I'm re-posting it on 12/3/7 in order for it be sent out for those of you who read the blog only via email.)

A Sebastiano Mercadante review is something that always catches my eye. He tends to be thorough and to look at the evidence critically. His recent article in Drugs and Aging on pain management in elderly cancer patients continues the trend. Edoardo Arcuri, a frequent collaborator, is co-author. Another Mercadante characteristic is a willingness to criticize other clinicians. The article cites, among the barriers to adequate management of pain in elders, a study finding that hospice nurses caring for the elderly "are almost twice as likely to incorrectly leave pain off a problem list than to incorrectly ascribe pain to a patient not reporting it." Even more pointed is a zinger at physician "unwillingness" to monitor opioid-related adverse effects.

The article also asks some important questions related to common assumptions about pain and elders: Do older patients feel less pain? Are they more sensitive to analgesics? In general, the answer to both questions is: the evidence is lacking, is unclear, or is contradicatory. The clinical bottom line, then, is: begin at lower doses than one would for younger adults, but be prepared to titrate to patient response. Unfortunately, they do not specify what "lower" means, but most clinicians start at 50% of the "usual" starting dose for opioids. They also say, however, that a cautious approach should not become one of "wasting time" when pain is acute. Pain can be aggressively managed and doses tritrated upward as needed as long as monitoring is frequent and appropriate to the patient's condition.

They particularly counsel caution with traditional (nonselective) NSAIDs because of the higher incidence of severe adverse effects as age increases. "NSAID renal toxicity may appear at lower doses in the elderly with subclinical renal insufficiency."

In the section on opioid elimination they point out that due to decreased muscle mass, serum creatinine is a less reliable predictor of glomerular filtration than in younger patients. Excretion may therefore be slower than predicted by serum creatine values.

Required skills for successful pharmacologic management of pain:

1. objectively assess functional age
2. understand the impact of coexisting conditions
3. carefully manage the number and type of medications taken concurrently
4. adequately communicate with patients and relatives

Other specific points:

• pain assessments and use of analgesics tends to decline as patients get older: those over 85 are at greater risk than those at 65, but there is no evidence that pain is experienced less


• there is great variability in physiologic and functional aging--the rate of decline is variable


• "the hypothesis that elders have a higher threshold for pain has not been supported"
• "no physiologic changes in pain perception in the elderly have been demonstrated"


• in general, elders require lower doses of opioids, but "only careful titration based on individual response can ensure that patients receive the level of analgesia that they require"


• elders do not have a greater incidence of side offects with opioids, but when they occur they tend to be more severe
• "the rate of drug delivery rather than the absolute dose over time was seen to influence both analgesia and side effects" (translation: increased dosing interval for immediate release opioids may be necessary)


• renal function is more important than hepatic function in the development of toxicity from morphine (glucoronidation can occur even in fairly advanced hepatic dysfunction)

It seems to be a common rule of thumb in this country (at least in the academic medical centers of my acquaintence) that hydromorphone is the preferred "first choice" opioid for elders or the first alternative should toxicities to morphine develop. This point is not even addressed in the article. Except for potency, they seem to indicate that morphine and hydromorphone are about the same. Oxycodone is recommended as a good alternative because the "pharmacokinetics of oxycodone are mostly independent of age, renal function, and serum albumin." Of course, parenteral oxycodone is available in Europe, but not in North America. Transdermal fentanyl is also said to be worthy of consideration for patients with chronic pain and reduced renal clearance, because it "might be better tolerated than morphine because of lack of accumulation of important metabolites." They caution, however, that the decreased lean body mass to fat ratio may may "facilitate fentanyl accumulation once fat and muscle stores are saturated."

This may be one of those articles to consider for Drew's famous Teaching File. It requires a close read, but provides an excellent "if you only have time to read one article" resource.

December 1 is World AIDS Day.

A research team at the Mayo Clinic presented findings this week at the meeting of the Radiological Society of North America on its study of cryoablation for pain resulting from metastatic bone tumors. 34 patients with 10 different tumor types were treated. 80% reported "clinically significant" pain reducation that persisted at 24 weeks after the procedure. Next up: a multi-institutional study that compares cryoablation head to head with radiation therapy.

A study (secondary analysis of a bisphosphnate study) published online ahead of print in Cancer this week again highlights the disparity between Caucasian and non-Caucasion patients in pain from advanced cancer. This study found that in a large international (19 countries!) cohort of women with metastatic breast cancer non-Causasian women (82% of whom were from the US) reached a pain level of 7 or higher (Brief Pain Inventory) significantly earlier than white women. They suggest that race be considered a risk factor for pain and that clinicians be prepared for aggressive and earlier intervention for pain in non-Caucasian women.

An article in the October issue of the Fordham Law Review uses the recent trial of a doctor accused of murdering/euthanizing her patients during the Katrina disaster to launch a discussion of intent and the use of "risky pain medication" at the end of life. It's pretty dense & legalistic (oh yeah, its the Fordham Law Review) but essentially defends judicious use of pain medication at the end of life (for pain) and "terminal sedation" [there are plenty of other terms that can be used; this one is particularly loaded] for intractable symptoms. Many people, of course, have raised the ethical issue that intent is difficult for a 3rd party to determine. In a criminal trial, a prosecutor has to convince a jury that the intent was to hasten death. My own opinion: since there is no evidence that appropriately titrated analgesics and sedatives hasten death--and evidence is accumulating (examples here and here) that they don't--double effect is not usually necessary as an ethical basis for defending the use of either class of drug in patients near death and experiencing severe symptoms.

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The Washington Post published an editorial on the drawbacks of living wills as powerful agents in advanced care planning. Well at least that is how the article started. The author of the piece, Charlotte Allen,was recently diagnosed with breast cancer, luckily caught in the early stages. The frustration of the piece stems from the omnipresent questions about living wills.

She felt "ever-so-slightly harassed" and imposed on by the frequency and style in which these questions were asked. So much so that she took these questions to come up with a conspiracy theory. The medical establishment and secular elitists want you to die. Now if you have read this post this far, I highly recommend you go read the primary article, because I am not going to re-hash it line by line here (see the end of this post for that). I do not recommend it as a fine piece of well-founded opinion writing, but I do recommend reading this piece, because I think this article represents a sizable minority view that is important for the medical field and palliative care especially to recognize.

In my early training in hospice and palliative care, I was excited by this new approach to medicine. Spending time talking with the patients and families, openly discussing difficult life and death topics with them so they could make the decisions that were in their best interest; these actions were very rewarding. But I did go through a brief militant hospice phase, where I thought hospice was 'right' for everyone, I just had to help them understand that. So I can see where Ms. Allen may see some of this over-bearing "accept death already, would ya?" style. From talking with more patients and families, I soon learned that hospice was not right for everyone. Some people need to fight to the very end. That is a good death for them. But because some want to treat to the end, it does not mean medicine has a death-wish for patients when we address end-of-life issues.

She impedes the full impact of this rhetorical exercise with the use of unnecessary pejorative words, broad generalizations, unfounded accusations, and setting up an artificial us against them divide. Readers familiar with Pallimed will know that we have outlined some of the limits of living wills, and surrogate decision making, so in part I agree with some of the points that Ms. Allen attempts to make. I just wish she did so in a much more factual way without using fear and smear tactics.

If you are really interested, I encourage you to read some of the entertaining 9+ pages of comments and the transcripts of a Q&A (much shorter than the comments). Most of the comments seem to oppose most of her points which I was glad to see that the readers of the Washington Post seemed to be well-informed. Most of the people who did agree with her broader accusations tended to side with her on opposing the outcome and decision making process of the Schiavo case.


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Some point by point issues with the article. This is kind of long. Well really long.

Use of fear as a anti-establishment tactic.

• I found something weasely...
• I've developed a sneaking suspicion that someone else may be hoping to call the shots
• "dying when we, the intellectual elite, think it is appropriate for you to die."

Who are the intellectual elite? Classic 'us vs. them' technique that leads to conspiracy theories. She answers later in the transcript that she defines the intellectual elite as: "Great minds at our universities and media."

• with the growing acceptance of such notions as physician-assisted suicide

See Drew's last post on public misperception on what euthanasia means. Polls on public acceptance of PAS vary widely and there has been no real trend in either direction that is well-established. Voter approval in one state 10 years ago, and with multiple failed attempts since then in other states, hardly makes the case for a growing approval.

• Many people, especially highly educated, nonreligious people, think that "physician-assisted death" is exactly the right way to go -- or to send off your unconscious mother.

What this has to do with highly educated or nonreligious people is unclear. It seems to be a dividing technique again, especially when "they" are thinking about doing this to Mom!

• American Academy of Hospice and Palliative Medicine reversed its long-standing opposition to physician-assisted suicide

A careful reading of this statement demonstrates that every attempt should be made to avoid PAS/PAD. And the Academy did not reverse its opposition, it has a position of studied neutrality. Reversal would be an endorsement, which this is not. Most of this I see comes from the fact that you have a national organization has to provide guidance to professionals in Oregon (legal PAS) and in other states (illegal PAS). There is research to show that PAS happens regardless of legality, but adhering to state laws or working to change them should be the approach to take if you do not like the way things are now.

• Have your doctor pull out your feeding tube or inject you with cyanide or do whatever fulfills your idea of death with dignity.

Now come on..."inject with cyanide?" That is really confusing the picture and equating that with stopping tube feeding is way too blunt for such a complex subject.
Misperceptions of medical language/approach.

• ...whether I would want to be denied "artificial" food and water...

Nutrition by mouth is considered natural. By other routes is artificial (feeding tube, IV, etc). Artificial nutrition is not inherently endowed as good. It must be used appropriately.

• ...being given 30 seconds in a busy lobby to read and sign a complex document...

True this is how the process starts, but quality medical establishments should take the time to address these with you after you have had time to review them. One should avoid making these decisions in haste or in a crisis when possible.

• ..."right to die"...
  

An ambiguous term at best. It is really more of a wastebasket term to lump subtle and complex ethical issues. It is difficult to throw this term out in the open without really defining it for the reader as to the author's understanding.

• Equating "good death/dying well" with the word euthanasia

These words all have very open meanings that have different understandings depending on circumstance and understanding. Good, death, dying, well are all common words with some overlapping themes. To suggest this is the secret medical code for 'hastened death' is disingenuous.

• "Then, what you have to do is take him to a hospice. That's what we did with my mother. They'll put him on a morphine drip, and he'll be gone in a few days. They know what to do."

Her first hand experience with hospice care is tainted by a strangers comments that could be interpreted in many different ways. Good hospice care may involve morphine drips, but the majority of hospice care does not need this measure to provide comfort. The rule should be the right dose for the symptom. Besides no one ever notes the fact that hospices have a financial disincentive to hasten death, they are often paid per diem. And I have had many, many patients live well and long on opioid drips.

• terminal sedation
  

Misperceived as sedating and then stopping food and fluids, when in fact most studies demonstrate that when this is enacted, the patient has often already stopped eating and drinking on their own.

• It's not surprising that many people have reservations about theories of "dying well" that always seem to involve not staying alive...only 18 percent of Americans of all races had them...

She again uses the possibility of the public reacting against the establishment as the potential reason for not having living wills. The most common reason I encounter in my practice: No one likes to talk/think/discuss end-of-life issues. That is a pretty obvious one.

The opinion piece's good points.

Many people do not have living wills. So let us better understand the barriers and help them pick a decision making process that is right for them.

Impotency of living wills. The process to make them and keep them up to date and readily available is a systems issue not a failure of the idea of a living will. Often the language is ambiguous, and the form is not updated frequently. POLST may be a way to fix some of these issues, but I am sure Ms. Allen would find some objections to that.

Living wills seem to only indicate what you don't want. That is true but that is a reaction to the perceived over-treatment by the medical system and how living wills were hatched in the first place. But there is no reason why a living will cannot say that your preferences are to be as aggressive as possible and to stop asking me about death and dying.
DPOA's are good things to have. They allow flexibility, but they also have limits and fallibilities that Ms. Allen neglects to highlight. Often they are signed without the most important discussion about wishes. Even when that happens surrogates may make different decisions.

She did not use the word narcotic. Pet peeve of mine.

I just want to die in peace. I think most people would agree with that. And that is what palliative care is about. Meeting you where you are at.

Picture Credit: Christian Sinclair, UC San Diego, "Bear"