Wednesday, August 30, 2006

Hydromorphone vs morphine for severe acute pain in the ED

Per the last post, here's a brief summary of the article. The study compared 0.015mg/kg of IV hydromorphone (1.5mg for a 100kg person) vs 0.1mg/kg IV morphine (10mg for a 100kg person). (They used the HM:M ratio of 1:6.67). Interestingly the background to this was that the authors, besides noticing that pain is often poorly treated in the ED, also noticed that people seemed reluctant to give the established dose of morphine for severe pain. They speculated that if they could promote HM as an effective analgesic, people would be more likely to use it because the milligram dosage is lower. This concept is clearly the theme of Pallimed for August, given this recent post. Sad but true. About 100 people were randomized in this well-blinded trial. It was a single instituion trial and most of the patients were Hispanic. The median pain score was 10/10. Patients receieved 'rescue' analgesia ad lib after the initial 'trial' treatment. Findings were essentially:
1) Hydromorphone decreased pain by 5.5/10 at 30 minutes vs 4.1/10 at 30 mins for morphine. This was borderline significant.
2) Hydromorphone definitely seemed to decrease pain more effectively (compared to morphine) for those with 10/10 pain: decreased by 5.9/10 compared to 3.7/10 at 30 minutes.
3) There was no differences in between groups at 2 hours including those with baseline 10/10 pain
4) Pruritis really did seem to occur more commonly with morphine (6% vs 0% although the numbers are small).
5) No significant adverse or safety problems were noted in this opioid naive population.

My gloss is that this supports the observation that morphine is one of the more pruritogenic opioids out there, and that the analgesic time-profile of morphine may be a little delayed compared to HM (this is not news). Finding #2 is interesting and deserving of investigation. Assuming all 'strong' opioids truly are equally effective analgesically, if this finding is validated it may cause us to tweak our understanding of HM:M potency. Of note, these were opioid naive patients, and extrapolation to the chronic opioid patient is difficult. The real story though is, like the other post, an apparent systematic underdosing of morphine, despite well accepted doses, presumably because 10mg is scarier than 1.5mg. This is a sad, but believable, state of affairs. Perhaps a campaign reassuring our colleagues that equianalgesia is a real thing--honest!--is needed. "Equianalgesia--believe it!" can be our motto. Christian, can you make up a logo?

Wednesday, August 30, 2006 by Drew Rosielle MD ·

Monday, August 28, 2006

Pressure ulcers; Out of hospital cessation of CPR; PCEP

Back from vacation, back at work, and already wondering how I can miss my baby boy so much after 9 measly hours.

Several things:

1)
There has been a randomized controlled trial comparing morphine with hydromorphone for acute pain in emergency departments.  I'm having trouble getting the full text of the article due to strange happenings at Science Direct (full text of the issue has not been posted although the full-text of the subsequent issue has already been put online...it's weird) but will get to it as soon as I can.  So few truly randomized, head to head trials comparing opioids in real patients in real pain using drugs I really use every day come out that it's always exciting to see if anything can be gleaned.  So stay tuned.

2)
JAMA has a systematic review of interventions to prevent pressure ulcers.  Can you guess the conclusions?  Lack of quality trials, heterogeneous methods and outcomes limit comparison, etc. etc.  These, though, were the major clinical findings:

Effective strategies that addressed impaired mobility included the use of support surfaces, mattress overlays on operating tables, and specialized foam and specialized sheepskin overlays. While repositioning is a mainstay in most pressure ulcer prevention protocols, there is insufficient evidence to recommend specific turning regimens for patients with impaired mobility. In patients with nutritional impairments, dietary supplements may be beneficial. The incremental benefit of specific topical agents over simple moisturizers for patients with impaired skin health is unclear.

3)
The NEJM recently published a report about out of hospital termination of cardiopulmonary resuscitation (that is, emergency medical personnel declaring a person dead and stopping resuscitative efforts in the field and bringing the deceased patient to a morgue and not an emergency department).  The study is actually a validation study of a rule (protocol) to predict who should have resuscitative efforts discontinued in the field, not a study of actually implementing cessation of resuscitation in a community.  The article follows ~1400 adults who arrested in the community and received resuscitative efforts and looks to see if the protocol rule accurately predicted those patients who didn't survive (such that, if implemented, people who would survive would not have resuscitation inappropriately terminated in the field).  The major elements of the rule is that 1) the arrest was not witnessed by emergency personnel and 2) the automatic external defibrillator device delivered no shocks ( i.e. the patient never had a 'shockable rhythm' like ventricular fibrillation).  These elements (along with a couple others) predicted accurately ~99.5% of deaths.  I'm not going to go into more details here about the actual protocol or the findings other than they appear to be quite robust.  What I want to mention is that this is one of several such protocols which are being developed and that in the not too distant future communities may begin implementing policies using these rules which will likely decrease the number of severely neurologically devastated people, headed to an inevitable death, ending up in emergency rooms and ICUs.  I am curious to see the public's reaction to this.  Surely a less than 1% chance of success/survival meets any reasonable definition of futility--no surgeon would operate if s/he thought the patient's chance of benefitting from the surgery was 0.5%--but things are different when it's CPR....

4)
The most recent Journal of General Internal Medicine has an article looking at the long-term impact of the Harvard Medical School Program in Palliative Care Education and Practice (PCEP).  Long term here means up to 18 months.  Generally they found that they made sustained behavioral changes in their participants.  So congratulations & it's good to see such positive, sustained results.

Monday, August 28, 2006 by Drew Rosielle MD ·

Friday, August 18, 2006

Pallimed goes on vacation; Katrina charges

I am travelling the upcoming week:  my first family vacation with a baby in tow.  Will likely post next in about a week's time.

Pat Malone, a nurse in Seattle, tried to leave these comments on the blog about the Katrina charges--blogspot apparently wasn't cooperating at the time so I told her I'd post her comments:

I am a nurse and I wanted to add an opinion to your blog but had trouble with the site.
 
I am very concerned about the arrests in New Orleans and how this will play out for the Palliative Care community.  I think all of us need to be very clear to separate routine end of life care and disaster planning.  This is a case of poor disaster planning on the part of the city, state and federal governments and our nursing and medical associations.
 
There are no standards for what to do in this kind of situation.  Period.  If we have a flu pandemic, for instance, we know we may not have enough ICU space and ventilators for everybody.  We learned from the Katrina victims that we are not prepared and we will learn from this case that we have no standards.  What do you do when you can't save everybody? We are na├»ve in this country.
 
I think one way to avoid this spilling over into setting better standards for routine end of life care is to communicate that separation.  This was a case of poor disaster planning.  End of life care during a disaster needs to be addressed and it needs to be addressed in the disaster planning arena.
Thanks for your blog and your work.


Happy August to all,

Drew

Friday, August 18, 2006 by Drew Rosielle MD ·

Saturday, August 12, 2006

Underdosing of morphine in hospitals; DEA; NPR

The current Pain Medicine has a few interesting articles...

1)
A brilliantly simple comparison of the dosing of IV morphine vs. hydromorphone vs. meperidine at a hospital.  The authors found that the median dose of morphine given was 2mg (!) wheras the median doses of hydromorphone and meperidine used were equivalent to 13mg and 7mg of morphine, respectively.  This is a great study because it demonstrates a major quality of care problem using simple methodology and outcomes, with dramatic results.  Would be curious to see if people think this is a problem at their institutions.  Besides not using meperidine at my institution, opioid equianalgesic tables are all over the place, on the opioid order forms themselves, etc., and while I do think this is a problem it's not quite as ridiculous as in this study. 

2)
There are also several articles about the ongoing debate/controversies surrounding DEA actions against pain docs.  There is one paper presenting data on the number of actions (suggesting they are miniscule) and a bunch of commentaries calling that bluff

3)
NPR this week had a few in-depth stories about the palliative care program at the Children's Hospital of Philadelphia.  Well worth listening to. 

Saturday, August 12, 2006 by Drew Rosielle MD ·

Friday, August 11, 2006

Methadone & the QT; Opioid switching; "Choosing" chemotherapy at the end of life

1)
Lancet has a brief communication about QT interval prolongation and high(er) dose methadone use .  This is further reminder that increased use of this drug as an analgesic may have unwelcome effects

2)
The Oncologist has a review on the pharmacology of opioid switching.  It reviews the small amount of evidence supporting its practice and also reviews the possible reasons why it may work (why do some people, idiosyncratically, seem to do better--fewer side effects, more pain relief--with some opioids compared to others).  No answers to be sure, but if reading about receptor polymorphisms gets you going it's worth reading.  Of note, however, the review furthers the confusion surrounding the terms potency and efficacy which creates sentences like this:

In terms of analgesia, all opioids should be equipotent, provided appropriate equianalgesic doses are used.

(This should read: ...all opioids should be equally effective, provided appropriate equianalgesic doses are used.)

3)
A recent Journal of Clinical Oncology article attempts to review the literature on why patients "choose" chemotherapy near the end of life.  I say 'attempts to review' because while this is ostensibly a review article, the literature is so heterogeneous and scarce that the article is more of a polemic about the current sad state of affairs when it comes to decision making about cancer treatments in advanced cancer.  It takes on a wide swath of issues:  frequently poor communication to cancer patients about prognosis and expected treatment outcomes; payment systems which deny reimbursement for family conferences; the evidence that patients learn more about their progression of disease and what to expect from other patients in cancer center waiting rooms than their physicians; the NCI website which lists radiosurgery and clinical trials as treatments for recurrent non-small cell lung cancer but not palliative care*; etc.  There is a common theme throughout the article of fear:  patients fearing death and wanting chemotherapy that (frequently) has no realistic chance of helping them & physicians fearing patients (patients' emotions, damaging patients' hope, etc.) and so not disclosing to them what is going to happen, what to realistically expect from their treatment, etc.

*This is the second article I've read in the last couple of weeks which trashes the patient information on the NCI website.

Friday, August 11, 2006 by Drew Rosielle MD ·

Friday, August 4, 2006

Delirium prognosis in JAGS

The current Journal of the American Geriatrics Society has prospective study on long-term outcomes for elderly patients with delirium during a hospitalization.  It prospectively looked at ~430 elderly (70 years and older; mean age 80) patients admitted to a non-ICU medical service at a single hospital who were, at some point during the hospitalization, diagnosed with delirium.  This study compares those who were never delirious with those who were discharged still delirious with those whose delirium had resolved.  It presents 1 year follow up data and they are confirmatory of delirium being a poor pr ognostic marker:  After one year 38% of those with delirium at discharged had died, compared with 26% with resolved delirium and 20% of those who were never delirious.  The study's composite outcome of death or nursing home placement was 83% for those delirious at discharge, compared to 68% and 42%, respectively, of the other two groups.  These trends were statistically significant when comparing the never delirious with the delirious at discharge group, although it's unclear to me whether they were significant comparing the resolved delirium with the never delirious group. 

In a related article the same issue presents a prospective study of outcomes after delirium associated with a stroke .  1 year mortality was markedly worse in the delirious patients than those who did not develop delirium:  41% vs 17%.  These two articles are further information of just how powerful a prognostic marker delirium is in these older populations.  It should be part of our calculus of identifying older people in particular need of palliative & advanced-care focused assessments and interventions.

(The same issue also has an article comparing patterns of home health and hospice use by older adults with cancer with those without cancer.)

Friday, August 4, 2006 by Drew Rosielle MD ·

Wednesday, August 2, 2006

Public's perception of cancer survivability; Phase I chemotherapy trials

Happy August & I hope you are staying out of the nation-wide heat-wave.

1)
The most recent Lancet Oncology has a narrative review on the public's perception of cancer survivability. It qualitatively surveys multiple reports on public understanding of cancer survivability and generally concludes that it is poor. The strongest trend they noted is a strong overestimation of lung cancer survivability and a strong underestimation of melanoma survivability. It's generally an interesting read, and places its results in the context of providers' difficulties in communicating prognoses to patients. An interesting phenomenon they discuss is cancer related websites' patient pages that generally paint positive pictures of cancer treatment & seem to "studiously avoid any reference to survival." They note that several of them have Questions for your doctor sections--few of which actually prompt patients to ask about survival or even treatment success. This includes the National Cancer Institute and American Cancer Society's websites!

Two more things to note about this article.... One, it is the first article I have seen whose search methods section begins with "
We searched Google and Google Scholar...." I can't say I endorse this trend. Second, it has this completely inexplicable graphic in the article:

(Ok well blogspot's image uploader won't work for me right now. The image is a drawn composite figure that looks like it was designed for Reader's Digest that has images of a labtech doing something unidentifiable to a wrack of test tubes; a geneaology diagram; a silhouetted family holding hands with green glowing splotches on their torsos which presumably represents radiation like it was a radionucleotide scan of some sort; and
a test tube with a cartoon DNA double helix floating out of it--this test tube is being held by what appears to be a wooden robot arm. I'm not making this up.)

The caption is
Cancer screening is generally viewed positively in the mass media. I can't for the life of me understand why this image was chosen or even drawn in the first place and it seems deserving of parody.

2)
Archives of Internal Medicine recently had an opinion piece arguing that one can argue sometimes that Phase I oncology trials have therapeutic intent. The background here is that traditionally Phase I drug trials have been conceived as 'first-in-human' trials of novel drugs whose only intent is to define the pharmacologic profile of the new agent as well as gather preliminary safety, dosing, & tolerability data. The point being is that there is no therapeutic intent to the trial--the subjects are not intended, personally, to benefit from being exposed to the trial drug. The authors here are arguing that some Phase I chemotherapy trials involve agents known to be beneficial in certain cancers, including cancers that the subjects may have--the trial is however looking at a novel combination therapy etc:

Thus, a phase 1 anticancer trial may be testing the safety and defining the appropriate doses and schedule of a novel combination of 2 well-established and known useful chemotherapeutic agents in a particular clinical setting.

The overarching theme of their argument is that subjects in Phase I trials should not, a priori, be told that the trial in which they are enrolling has no therapeutic intent. This certainly seems reasonable, under some circumstances, although not being a chemotherapy trialist I'm not sure that there is this a priori practice of forewarning all Phase I subjects that their participation in the trial has zero therapeutic intent. That is, I'm wondering if this is a rhetorical straw-man set-up by the authors to make a point. Leave a comment if you know have any light to shed on this.

Wednesday, August 2, 2006 by Drew Rosielle MD ·

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