In a short article in American Journal of Hospice and Palliative Medicine a palliative care team in India describe their observation that some patients who did not experience constipation while receiving IV morphine required laxatives for constipation when converted to oral morphine. They did a 5-month retrospective chart review and found 11 patients who did not experience constipation while on moderate doses of intravenous morphine. They had a pretty "clean" sample: opioid-naive patients admitted for severe pain, no malignant or comorbid GI pathology, not using laxatives prior to admission. When switched to equianalgesic doses of oral morphine, 7 of the 11 patients required laxatives for the remainder of their inpatient stay and were discharged on laxatives.

The New England Journal of Medicine recently had a case series and several editorial (here, here, and here) about organ (heart) donation after cardiac death ('DCD') in infants. All articles are available as free full-text. DCD describes the practice of procuring organs from a patient after he/she has been declared dead based on their heart stopping beating after life-support such as a ventilator and pressors are stopped (as opposed to them being declared dead based on brain death criteria which is, currently, the most commonly used method). The series describes one center's experience with this in 3 infancts, the protocol used, and some basic outcomes (for the heart transplant recipient infant - which were generally good).

The editorials highlight some interesting points, and I learned a lot, especially as I assumed I was one who was supposedly well-informed about the major issues surrounding DCD. These cases involve heart transplantation and it's apparently controversial to transplant hearts after DCD. (the simplified version of the argument being that one is declaring someone dead because their heart has, supposedly, irreversibly stopped beating - if you go on to transplant the heart then clearly that organ was not permanently non-functional - of course it may have been permanently non-function in that patient's body due to other causes...). And thus there is a debate if whether death should be declared after there is no chance of 'auto-resuscitation' (the heart spontaneously resumes beating on its own) - which anecdotally is in the 1-few minutes range depending on the population.

Further confusing variations in DCD practices are also described (in this editorial):

Another unconventional protocol used by several hospitals for donation after circulatory death involves providing ECMO to the donor immediately after death is declared. If ECMO adequately provided circulation and oxygenation to the donor's entire body, it would retroactively negate the death determination by preventing the loss of circulation and respiration from becoming permanent or irreversible, potentially "reanimating" the heart and preventing the progression to brain destruction on which the circulatory criterion of death is predicated. A University of Michigan ECMO protocol for procuring abdominal organs apparently avoids this problem. During ECMO, an intraaortic occlusion balloon blocks all blood flow above the diaphragm so that only the abdominal organs are perfused with oxygenated blood. The thoracic organs and brain are isolated from this perfusion circuit and are destroyed by ischemic infarction. If blood flow above the diaphragm is successfully blocked, this protocol does not negate the previous determination of death. Ex vivo ECMO, in which the procured organ is temporarily perfused and preserved after removal from the donor's body, is another technique that is under investigation.

What has been the cost of our continued dependence on the dead donor rule? In addition to fostering conceptual confusion about the ethical requirements of organ donation, it has compromised the goals of transplantation for donors and recipients alike. By requiring organ donors to meet flawed definitions of death before organ procurement, we deny patients and their families the opportunity to donate organs if the patients have devastating, irreversible neurologic injuries that do not meet the technical requirements of brain death. In the case of donation after cardiac death, the ischemia time inherent in the donation process necessarily diminishes the value of the transplants by reducing both the quantity and the quality of the organs that can be procured. Many will object that transplantation surgeons cannot legally or ethically remove vital organs from patients before death, since doing so will cause their death. However, if the critiques of the current methods of diagnosing death are correct, then such actions are already taking place on a routine basis. Moreover, in modern intensive care units, ethically justified decisions and actions of physicians are already the proximate cause of death for many patients — for instance, when mechanical ventilation is withdrawn. Whether death occurs as the result of ventilator withdrawal or organ procurement, the ethically relevant precondition is valid consent by the patient or surrogate. With such consent, there is no harm or wrong done in retrieving vital organs before death, provided that anesthesia is administered. With proper safeguards, no patient will die from vital organ donation who would not otherwise die as a result of the withdrawal of life support. Finally, surveys suggest that issues related to respect for valid consent and the degree of neurologic injury may be more important to the public than concerns about whether the patient is already dead at the time the organs are removed.

Annals of Internal Medicine has a narrative review of the use of furosemide for hypercalcemia, a syndrome which is unfortunately not uncommon in advanced cancer patients. Its conclusion is straight-forward: it has no role in the treatment of hypercalcemia (which should instead be saline hydration, bisphosphonates, +/- calcitonin). Towards the end of it there are some philosophical remarks about evidence:

We show that despite more than 20 years of careful phase I to III research supporting saline hydration with bisphosphonates as the preferred first-line therapy in hypercalcemia and the lack of significant supporting evidence for furosemide, this medication continues to be routinely recommended for emergency management. As recently as 2005, a review recommended 20 to 40 mg of furosemide after adequate hydration; the author acknowledged that this was based on "historical precedent and common practice." Reliance on historical precedent is not limited solely to the management of hypercalcemia; many therapies have become habit, often without supporting evidence. We may not know where such a habit came from and may struggle to find its origin; however, that search may be informative and practice-changing. Such a search may have several possible outcomes: No evidence is found to support the current recommendations, leading to a new standard of care; limited but supporting evidence is found that argues for additional studies; or adequate evidence is found to support the existing precedent. We argue that our search of furosemide studies is an example of the first outcome.

Pain Medicine has a trial looking at cognitive changes when transitioning chronic non-malignant pain patients from short-acting to long-acting opioids. It involved ~120 adults on short acting opioids (over 80% were on 60mg/day of oral morphine equivalents or less) who were transitioned to approximately equivalent doses of sustained-release morphine (once daily formulation). (Curiously, methadone was treated as a short acting opioid in this study.) They looked at pain, depressive symptoms, and cognitive function (using things like the digit span test) before and after the rotation to once-daily morphine and found that everything got a little better (pain/depressive symptoms) or stayed the same (cognitive functioning). So hooray for once daily morphine.

The problem however is that ~40 patients were deemed 'non-evaluable' (yes, a 3rd of the cohort!) and the outcomes were only presented for those 'evaluable' patients (and it's unclear what happened to those non-evaluable patients or why they were non-evaluable): so the message is I guess that your opioid-tolerant patients who tolerate/go along with 1 month of a rotation to once-daily morphine...well, that they tolerate once-daily morphine.

This was an industry-sponsored study which didn't really go into why they 'lost' a third of their study group (which happens sometimes we all realize but not even telling us why/how really makes you question everything about the study). Especially since the world doesn't necessarily need more proof that many opioid-tolerant patients tolerate opioids (!) - but understanding more about how/why some patients do not tolerate a switch to equivalent doses of a long-acting morphine - that's something we do need to understand better.

There is an interesting pair of studies in Quality Management in Health Care on the use of a simple Microsoft Excel-based simulation tool for teaching medical residents to manage pain crisis in cancer inpatients. The authors had previously determined through surveys of residents and nurses that residents were unprepared for and uncomfortable with managing pain with opioids. Specifically, they were afraid of respiratory depression, especially with escalating doses and long-acting opioids, and had no preparation for converting to other routes or drugs. The informal practice was to manage all cancer pain with intermittent short-acting opioids. The result was that patients complained of uneven pain control marked by "peaks & valleys" and that average pain scores actually increased among hospitalized cancer patients. Not surprisingly, patients, residents and nurses were dissatisfied with pain management. Outcomes, by the way, were unchanged following standard educational interventions such as grand rounds presentations.

The authors then developed a "case-based Microsoft Excel program with an interface from which the user selects from a list of medications, orders a dose, and chooses a follow-up interval to assess pain response." Cases are based on 15 actual patients who had been admitted for treatment of pain exacerbation. All opioids, doses, and times given, and pain score responses for these patients were entered. I'm unclear as to what happened next [I'm not a math or computer guy]. Noting that "patients did not respond the same to any given dose of narcotic" [the grinding teeth you hear are mine] they somehow, using a variety of sources, derived a range of "sensitivities of response to equivalent morphine doses." Operationally, they applied a random number generator to select a sensitivity to each starting dose applied to each patient. One hundred sensitivities are possible. Applied to the 15 patients, this translates to 1500 different cases.

The interface provides a dose-response curve that shows the user what happened when a dose was administered in a particular case. If the user chooses a reassessment interval that is too long, the graph may trend back up into higher pain scores.

The graph above shows one possible dose-response curve for a single dose of opioid. As the case develops, the curve reflects response to all doses over time (48 hours in this study).

Principles of care taught didactically, then reinforced by simulator (Goal: rapid induction of pain relief):

• morphine is the default opioid (ok, so I translated the archaic "narcotic" to the preferred modern term)
• do not define a specific starting dose; instead, assess, start low, rapidly titrate using early close follow up to each dose
• use standard conversion table
• reassess every 30 - 60 minutes during titration
• convert to long-acting opioid as soon as possible ("early in care") to stabilize pain and medication regimen
• use 8-hour intervals for long-acting agents

I won't go into the details, but they tested the simulator against seven actual patients admitted solely for pain control and found that the pre-determined dose-responses programmed into the simulator included those exhibited by the patients. In a pilot study 31 residents completed 2-3 simulations. Results were independently evaluated by 7 reviewers. The finding was that 90% of the residents improved their pain care.

A follow up study (the 2nd article) of several small groups of residents entering their oncology rotation showed that, after simulator training, pain scores--of actual patients they cared for on the oncology unit--decreased (over the first 48 hours after admission for pain control), more patients were prescribed long acting agents, and less naloxone was used.

We have known for many years that providing information alone, and that teaching skills such as safe opioid conversion, does not translate into improved pain control. Even a standard case-based approach is not "real" enough for clinicians to apply the critical thinking and get the feedback they need in order to overcome the endemic fear these drugs evoke. The approach these articles describe is a relatively simple, relatively inexpensive intervention that allows barriers to be broken down in a safe environment.

It wasn't always clear when the authors were describing intravenous vs oral medication administration. But if the reassessment interval for intravenous and oral opioids was the same (30-60 minutes), the patient receiving the intravenous medication is potentially left in unnecessary pain long after the peak effectiveness could have been assessed. In the first article the authors stated that nurses and residents are the primary care providers for patients on the oncology unit. There was no description of the clinical role that nurses played in the care of patients in pain. It is pretty clear to most of us that "the team" needs to include the bedside nurse. The early reassessment of intravenous opioid administration is surely part of the nursing role.

References:

1. Harting B, Hasler S, Abrams R, Odwazny R, McNutt R. Computer-based simulation as a teaching tool for residents treating patients with cancer-related pain crises. Qual Manag Health Care. 2008 Jul-Sep;17(3):192-9.

2. Harting B, Abrams R, Hasler S, Odwazny R, McNutt R. Effects of training on a simulator of pain care on the quality of pain care for patients with cancer-related pain. Qual Manag Health Care. 2008 Jul-Sep;17(3):200-3.

Several news agencies and likely your local TV news (but curiously not the NY Times, Washington Post, or Wall Street Journal) had articles in the past week highlighting the online publication of a nationwide hospital mortality database from Medicare data. The information is drawn from inpatient mortality rates from heart failure, myocardial infarctions (heart attacks) and pneumonia cases. Drew commented last year on a JAMA article last year about the usefulness of mortality rates as quality indicators.¹

Note: inpatient mortality is qualified as dying within 30d of hospital admission regardless of location of care at time of death.

Let's consider the ways palliative care can affect the inpatient mortality rate for any of these three conditions:

First, does a hospital have a palliative care team?
Your hospital may fear adding a palliative care team because it may errantly believe palliative care will increase their inpatient mortality rate. But one must consider that an effective palliative care team can facilitate safe and appropriate discharge plans, that can reduce unneeded readmission due to system errors, and by connecting patients with helpful outpatient services such as hospice.

Second, does a hospital have an effective, multi-disciplinary team that has wide penetration across diagnoses and clinical services?
A palliative care team that only sees patients in the ICU or oncology floor may not have a hospital wide impact on these three diseases. So therefore any effect on the inpatient mortality rate may be minimized

Third, does your hospital administration know that any patient who is receiving goals of comfort care is excluded from this mortality rate?
Here is the language from the Joint Commission Appendix on Hospital Quality Measures:

Beginning with patients discharged in July 2006, patients receiving only comfort care (support for the dying patient) were excluded from all of the heart attack and heart failure measures. This exclusion had previously been applied only in the pneumonia measure population. With the addition of this exclusion in the heart attack and heart failure measure population, it is likely that some actual measure rates may change from previous reporting periods.

Physician/nurse practitioner/physician assistant document that the patient was receiving comfort measures only. This is commonly referred to as “palliative care” in the medical community and “comfort care” by the general public. Palliative care includes attention to the psychological and spiritual needs of the patient and support for the dying patient and the patient's family. Usual interventions are not received because a medical decision was made to limit care to comfort measures only. Comfort Measures only are not equivalent to the following: Do Not Resuscitate (DNR), living will, no code, no heroic measure.

In the July issue of the Journal of Palliative Medicine, there was a brief news note on how to prepare for the upcoming Palliative Medicine Boards. There was a lot of good advice in there about reviewing the outlined content for the exam, becoming familiar with review courses* and review materials, and the upcoming HPM Pass practice exam**.

There was even mention of some great online resources like EPEC-O, Fast Facts, the Palliative Care Journal Club and Pallimed. Except that Pallimed was not listed as a good tool for reviewing for the boards. Well, I want to tell you I think Pallimed is a great free tool to review for the boards. Obviously, I am a bit biased. And of course, I mean no disrespect to the others, since I reference them often!

But honestly if you are looking at using Pallimed as a Board Review resource I would not advise solely depending on Pallimed unless you have a good foundation of palliative medicine basics. With 3+ years of reviews of the important literature for palliative care right here at your fingertips I don't think it will hurt your score at all.

Let us know in the comments if you are using Pallimed to review for the boards, or what other resources you find most helpful. I seem to be getting a lot more emails lately about how to review for the boards, so maybe the community might help answer this better.

If it could be shown, I would bet all Pallimed readers would score higher on the boards then non-Pallimed readers, because you are all smart enough to be here. You are also very good-looking.

For full disclosure:
*Disclaimer: I am speaking at the Current Concepts course (Aug 08) and receiving speaking fees. Feel free to come say hello on Thursday!
**Disclaimer: I am a reviewer for the HPM Pass questions but am not receiving fees.

1. NYT on Choosing Chemo
Jane Brody highlights how tough it is to make decisions about a chemotherapy plan in the New York Times. The article makes reference to the JAMA article about chemotherapy at the end of life we had blogged about in June. (HT: Hospice & Caregiving Blog from HFA)


2. Best Blog Post Title of the Year Nominee

Methadone for cancer (no) and cancer pain (yes)

I said, "You must never come back."
He said, "I have left my mark upon you. I will return some day to claim what is mine."
I said, "But you have left me with nothing."
He said, "Until I come back, I leave my curse upon you. You will no longer hope for the future, for every day you will fear my return. I will be in your thoughts and in your dreams. I am already so much a part of you that you will not feel alive without me. In my absence, I will still be your master."

As the days went by, I felt strangely empty.
As the weeks went by, I began to seek him out so that I would once again feel alive.
As the months went by, I entered the pit of depression, and anger ruled me.
As the year past, I felt I was already dead and wanted to end it all.

Multiple news organizations have recently highlighted the release of aging and terminally ill prisoners back into the community. Of course if you have very sick and possibly dying people coming into your community one of the services they may need is hospice. While in the prison system, the health care is paid for by the government, but once they leave the prison, they have to find their own coverage most likely through Medicare (if eligible), but of course there is a very good chance they may not ever get any coverage. The main focus of the news articles is the ballooning cost of health care for prisoners.

Many hospice agencies are likely to get at least a few referrals from recently released prisoners, which brings up many logistical issues about safety, potential charitable coverage for their care, addiction or diversion concerns, and possible complex family dynamics with the reintroduction of the person back into the family. These issues can come up in any hospice admission of course, but this unique situation may take some detailed care planning on the part of the hospice team.

Interestingly, few of the articles highlighted the role of prison hospice, which was featured in a excellent JAMA article last year. The focus on medical release for terminally ill patients was relegated to two paragraphs at the end of the article. The article cited a stat on average 8 of 18 annual requests are granted for release secondary to a terminal illness.

For our field, it can pose a major dilemma. Do we advocate for the well-being of our patient to possibly return home despite being a criminal who has not completed their given sentence? How do we compare our duty to the patient versus the societal justice and completion of the punishment accorded the prisoner? Should it matter what the offense is for?

Reference:
Linder, J.F., Meyers, F.J. (2007). Palliative Care for Prison Inmates: "Don't Let Me Die in Prison". JAMA: The Journal of the American Medical Association, 298(8), 894-901. DOI: 10.1001/jama.298.8.894 (free access with JAMA registration)

Drew is on vacation so I get to post on this open access article just published in the BioMed Central Palliative Care Online Journal. The article examines the uses for the Cochrane Reviews, a favorite of Drew and Tom. Since they have long lamented the general lack of clinical usefulness of the Cochrane Systematic Reviews in Palliative Care, I am thinking they should at least get an acknowledgment in the paper.

The authors looked at the 25 palliative care oriented Cochrane Systematic Reviews and found that they all looked at heterogeneous study designs, heterogeneous populations, heterogeneous outcomes, et cetera...et cetera. Therefore any clinical recommendations were weak or neutral. So what we are left with is the classic tired coda for any research paper or presentation. Say it along with me...